ANTITOXIC EFFECTS OF GUM ARABIC (ACACIA SENEGAL) AND GUAR GUM (CYAMOPSIS TETRAGONOLOBUS) AGAINST HEPATORENAL TOXICITY INDUCED BY MERCURIC CHLORIDE IN RATS

ANTITOXIC EFFECTS OF GUM ARABIC (ACACIA SENEGAL) AND GUAR GUM (CYAMOPSIS TETRAGONOLOBUS) AGAINST HEPATORENAL TOXICITY INDUCED BY MERCURIC CHLORIDE IN RATS

Amira Abd El-Rhman * and Nehad Naem Hamed Shosha

Department of Biochemistry and Nutrition, Faculty of Women for Arts, Science and Education Ain Shams University, Cairo, Egypt.

ABSTRACT: Heavy metal accumulates mostly in the liver and kidney as these organs involved in the detoxification and excretion of foreign materials. In the present study, we explored the effect of Gum Arabic (GA) and Guar Gum (GG) on mercuric chloride (HgCl₂) induced hepatorenal toxicity. Twenty-eight adult male albino rats “Sprague Dawely” weighing 250-300 g were divided into four equal groups: the first group served as the negative control group, the second group received intraperitoneal (I.P.) injection with HgCl₂, the third group received HgCl₂ injection followed by GA and the fourth group received HgCl₂ injection followed by GG. HgCl₂ injection caused a significant increase in serum total bilirubin, aspartate aminotransferase (ALT), alanine aminotransferase (AST), creatinine, urea, and uric acids compared to control. Moreover, there was a significant reduction in tissue-reduced glutathione (GSH) with a marked increase in the tissue hydroxyproline content and TGF-β% in the liver and kidney. Also, hepatorenal intoxication was confirmed by histopathological examination compared with the control group. Treatment with GA or GG showed significant recovery (p ≤ 0.05) in all previous parameters and histopathological appearance. In contrast, GG showed more powerful improvement than GA. In conclusion, we suggested that GA & GG may have a promising antitoxic property, gives it the applicability to be used as a prophylactic agent against mercury-induced hepatorenal cytotoxicity.

Keywords: Mercuric chloride, Gum Arabic, Guar gum, Hepatorenal, Toxicity

INTRODUCTION: Mercury (Hg) is a global environmental pollutant, accumulating mainly in the kidney and liver inducing hepatorenal toxicity, oxidative stress, and tissue damage ¹. Exposure to any form of mercury from different ways such as water, air, soil, and food poses serious threats to our health and the environment ².

Mercury ions are taken up and accumulate in numerous organs, including the brain, intestine, kidney, liver, and placenta ³. One reasonable hypothesis of mercury toxicity that it is involves oxidative stress, inflammation, and apoptosis ⁴.

High Hg exposure can trigger the formation of Reactive Oxygen Species (ROS) and interfere with the body's antioxidant metabolism. A high level of free radicals in the body can be characterized by a low level of an antioxidant enzyme ⁵. The uptake, accumulation, and toxicity of inorganic Hg in the liver and kidney have been related to its binding to endogenous thiol-containing molecules. Considering that oxidative stress and endogenous thiol depletion are involved in inorganic Hg toxicity, it has been suggested that antioxidants could contribute to the treatment of Hg poisoning ¹.

Gum Arabic (GA) belongs to the “Fabaceae” plant family, also known as gum acacia. GA is a dehydrated sticky exudate gained mainly from the stems and branches of Acacia Senegal, it is water-soluble dietary fibers, consists principally of polysaccharides with high molecular weight and their magnesium, calcium, and potassium salts, the viscosity effect of these fibers relays digestion and absorption of carbohydrates, regulating glycemic index and bodyweight reduction ⁶. GA suppresses absorption of glucose in the intestine via interaction with membrane abundance of sodium-glucose transporter-1 (SGLT1) in experimental mice ⁷. GA possesses antioxidant, antihyperlipidemic, and antidiabetic effects ⁸. Moreover, phenolic compounds, ferric reducing power, and cupric reducing capacity was detected in GA samples ⁹. This antioxidative capacity enables GA to exert protective effects on liver and kidney organs ¹⁰.

Guar gum (GG) bean is found mostly in India, Pakistan, U.S., Australia and Africa. It is a high molecular weight polysaccharide that is chemically composed of sugar galactose and mannose. The backbone of this polysaccharide is a linear chain of β 1,4-linked mannose residue while the galactose residues are 1,6-linked at every second mannose, giving short side branch ¹¹. Guar gum has been widely used in the food industry as a thickener and/or emulsion stabilizer based on its excellent solution properties ¹². However, a highly viscous GG solution can interfere with digestion and absorption of nutrients, resulting in reduced protein efficacy and lipid utilization ¹³. Guar gum (GG) acts frequently as water-soluble and bulk-forming laxative fiber. It is effective in promoting regular bowel movements, relieving constipation, Crohn’s disease, diverticulosis, irritable bowel syndrome and colitis, etc. Guar gum and its derivatives can be employed for physiological disorders ¹⁴. The intake of partially hydrolyzed guar gum (PHGG) reduces the postprandial blood glucose absorption in the small intestine and glucose level in the systemic circulation ¹⁵. Moreover, extremely high viscosity restricts the incorporation of GG into enteral formulas or food products at a physiologically effective concentration to show positive health benefits ¹⁶. This study aimed to evaluate the antitoxic effects of GA and GG against hepatorenal toxicity induced by mercuric chloride in rats.

MATERIALS AND METHODS:

Materials: Gum Arabic and Guar Gum were purchased from the Agriculture Research Center, (Giza, Egypt). They were purified and screened out from any impurities. The water solution was prepared by adding distilled water to the powder of GG and GA to achieve a dose of (500 mg/kg body weight) ¹⁰.

Chemicals: Mercuric chloride was obtained from El Gomhoreya Company for Drugs Trade& Medical supplies, Cairo, Egypt.

Animals: Twenty-eight adult male albino rats “Sprague Dawely” weighing 250-300 g were kept in stainless steel cages in the well-ventilated animal house of the Medical Ain Shams Research institute (MASRI), Faculty of Medicine, Ain Shams University. All rats had been kept in the room for 1 week before the beginning of the experiment for acclimatization. All experiments were conducted in accordance with the guide for the care and use of experimental animals for maintenance, treatment, and killing of the animals.  Animals were housed in stainless cages and provided a commercial diet and water ad-libitum.

The experiment was designed and conducted according to bioethics approved by the animal care use committee (IACUC) of Faculty of Science, Cairo University No: 1607 on 3/7/2020.

Induction of Hepatorenal Toxicity: Rats were injected I.P. by 4 mg/kg HgCl₂ as a single dose 1.

Experimental Design: The animals were divided into four groups 7 rats in each group. Group 1: (control group) rats were injected I.P. by normal saline as a single dose then received 1ml distilled water daily using oral gavage for 2 weeks. Group 2: (HgCl₂ group) served as positive control injected by Hgcl₂ as mentioned before for induction of hepatorenal toxicity then received 1 ml distal water using oral gavage daily for 2 weeks. Group 3 (HgCl₂+GA) & Group 4 (HgCl₂+GG) rats were injected by HgCl2 as group 2 followed by 1ml oral dose of GA or GG water solution respectively at a dose of (500 mg/kg body weight) 12using oral gavage daily for 2 weeks.

Sample Collection: At the end of the experimental period (2 weeks), all animals were sacrificed by cervical decapitation and blood samples were collected from the hepatic portal vein. Blood was left to clot and serum was separated by centrifugation at 3000 r.p.m. for 10 min at 4 °C where the clear serum was obtained for biochemical analysis. Liver and kidney were removed, washed with saline solution, dried then part of tissue samples was and kept in 10% formalin solution for microscopic examination, and another part used for determination of reduced glutathione, hydroxyproline content and TGFβ^-1.

Biochemical Analysis: Liver function tests such as serum ALT, AST enzyme activities, and serum total bilirubin were determined. Also, serum urea, uric acid, and creatinine levels were determined to assess kidney functions using colorimetric Bio-Systemskits (BioSystems S. A. Costa Btava, Spain) according to the manufacturer’s instructions.

Liver and kidney tissue homogenate were prepared by rapidly homogenizing (Use Dounce Tissue Homogenizer Cat. No.PK-CA577-1998) and used for determination of GSH level, using colorimetric assay PromoKine kits IC at. No. PK-CA577-K464 (Sickingenstr. Hiedelberg, Germany). Also, tissue TGFβ-1% was measured by sandwich ELISA assay for quantitative measurement using BioVision TGFβ^-1 (Rat) ELISA Kit Cat. No. #E4510-100 (Milpitas Blvd., Milpitas USA).

Furthermore, Hydroxyproline in liver and kidney tissue was determined by colorimetric assay using BioVision hydroxyproline Kit (Perchlorate-Free) Cat. No. #NBP2-59747) USA.

Histopathological Examination: Formalin-embedded liver and kidney tissues were cut into 4 μm thick sections, and then, the slides were stained with hematoxylin and eosin (H&E) for histological. Sections were examined and photographed using an Olympus light microscope (Olympus BX51, Tokyo, Japan).

Statistical Analysis: Data were statistically analyzed by Statistical Package for Social Science (SPSS) version 16.0 statistical packages. Values were presented as mean ± standard deviation (S. D). Statistical differences between groups were performed using one-way ANOVA; the mean difference was significant at the level (p<0.05) level ¹⁷.

RESULTS:

Antitoxic Effects of Gum Arabic (Acacia Senegal) and Guar Gum (Cyamopsis tetragonolobus) on live status: From the results tabulated in Table 1 it was clear that I.P. injection with HgCl₂ caused acute liver toxicity that appeared as a significant increase in serum total bilirubin level that recorded 0.541±0.178mg/dl while the normal control group recorded mean value 0.116±0.010mg/dl. Also, liver enzymes ALT and AST showed a significant increase as the mean values were 77.37±15.530 U/L and104.11±4.70 U/L, respectively.

TABLE 1: ANTITOXIC EFFECTS OF GUM ARABIC (ACACIA SENEGAL) AND GUAR GUM (CYAMOPSIS TETRAGONOLOBUS) ON LIVER STATUS

Values are represented as mean ±SD., (n=7) There was no significant difference between means that have the same letter in the same column (P< 0.05)

While their corresponding controls were 21.63 ± 5.030 U/L and 42.39 ±1 .35U/L, respectively. The oral administration of water solution of GA showed a significant decrease in serum total bilirubin level and liver enzyme activities ALT and AST by about 52.5%, 51.5%, and 13.5%, respectively as compared with HgCl₂ group. Meanwhile, the oral administration of water solution of GG caused a more significant decreased in serum total bilirubin level and liver enzymes ALT and AST activities by about 59.33%, 60.5%, and 25.6%, respectively, as compared with the HgCl2 group.

The results of liver homogenate analysis for GSH level showed a significant decrease inHgCl₂ group that recorded 0.271 ± 0.029 nmol/mg while the corresponding normal control mean value was 0.495 ± 0.050 nmol/mg. Treatment with GA and GG caused a significant increase of reduced glutathione level where the mean values were 0.883 ± 0.029 nmol/mg and 0.709 ± 0.014 nmol/mg respectively. With respect to the result of hydroxyl-proline (HPR) in liver homogenate, the normal control group recorded 0.69 ± 0.054 µg/mg while I.P. injection with HgCl₂caused a significant increase that recoded 3.06 ± 0.147 µg/mg. Oral administration of GA and GG decreased significantly the mean values of HPR by about 35.29% and 41.18%, respectively, as compared with HgCl₂ group. The results of TGFβ^-1 showed the normal control level was 4.65±1.65 pg/mg while HgCl₂ injection caused a significant increase that recoded 9.99 ± 0.96 pg/mg. Moreover, treatment with GA and GG caused a significant decrease in TGFβ^-1 level in liver homogenate by about 40.34% and 44.94 %, respectively, as compared with HgCl₂ group.

Antitoxic Effects of Gum Arabic (Acacia Senegal) and Guar Gum (Cyamopsis tetragonolobus) on Kidney Status: The present results tabulated in Table 2 showed that the I.P. injection with HgCl2 caused acute kidney toxicity that appeared as a significant increase in serum levels of NPN components creatinine, urea, and uric acid that recorded mean values 3.74 ± 0.132 mg/dl, 81.45 ± 6.50 mg/dl and 2.24 ± 0.163 mg/dl respectively while, their corresponding normal control mean values were 0.39 ± 0.045mg/dl, 34.61 ± 0.05 mg/dl and 1.14 ± 0.107mg/dl respectively.

TABLE 2: ANTITOXIC EFFECTS OF GUM ARABIC (ACACIA SENEGAL) AND GUAR GUM (CYAMOPSIS TETRAGONOLOBUS) ON KIDNEY STATUS

Values are represented as mean ±SD., (n=7) There was no significant difference between means that have the same letter in the same column (P< 0.05)

The oral administration of GA showed a significant decrease in serum levels of creatinine, urea, and uric acid by about 49.73%, 36.35%, and 50 % respectively as compared with HgCl₂ group. Whereas, oral administration of GG significantly reduced their serum levels by about 47.06%, 52.90%, and 46.43%, respectively as compared with HgCl₂ group. The results of kidney homogenate analysis for reduced glutathione level were 0.42 ± 0.036 nmol/mg in the normal control group while injection with HgCl₂ significantly reduced the level to 0.33 ± 0.013 nmol/mg. Treatment with GA and GG caused a significant increase of reduced glutathione level in kidney homogenate and mean values were 0.65 ± 0.018 nmol/mg and 0.79 ± 0.018 nmol/mg, respectively.

As noticed GG was more effective than GA on GSH level. Concerning the result of HPR level in kidney homogenate, the normal control group recorded 1.42 ± 0.021 µg/mg while HgCl₂ group significantly increased the level to 4.79±0.264 µg/mg. Oral administration of GA and GG significantly decreased the mean values of HPR that recorded 3.86 ± 0.144 µg/mg and 4.03 ± 0.072 µg/mg, respectively. The results of TGFβ^-1 in kidney homogenate showed that the normal control level was 10.84 ± 0.370pg/mg while injection with HgCl₂ caused a significant increase that recoded 24.45 ± 4.400pg/mg. Moreover, treatment with GA and GG caused a significant decrease in TGFβ^-1 level by about 53.17% and 54.31%, respectively, as compared with HgCl₂ group.

Histopathological Examination of Liver and Kidney Tissues: According to the results of histo-pathological examination of liver and kidney tissues that were illustrated in Fig. 1 & 2, there were no abnormalities or histological changes observed in the livers of normal rats as illustrated in Fig. 1A that showed normal central vein in some of the hepatic lobules. In addition, unremarkable hepatocytes and portal tract concluded unremarkable changes in liver tissue.

While HgCl₂ injection caused severe hepatic necrosis with disappearance and dis-arrangement of hepatic lobules structures. Extensive granular and vesicular degeneration, vacuolation, and inflammatory cell infiltrations in the portal region in the liver were also observed Fig. 1B, 1C & 1D illustrated that treatment with GA, and GG showed some regions of recovery and restored the normal architecture of the hepatic lobules and the hepatocytes.

FIG. 1: HISTOPATHOLOGICAL FINDINGS IN THE LIVER. (A) HEPATIC HISTOLOGY OF THE CONTROL GROUP, SHOWING NORMAL HEPATIC LOBULAR ARCHITECTURE. (B) HEPATIC DEGENERATIVE CHANGES WITH EXTENSIVE CELL NECROSIS WERE OBSERVED INHGCL2 INJURED RATS. (C) GA TREATED GROUP SHOWED MILD CHRONIC NECROSIS (D) GG TREATED GROUP SHOWED A SIGNIFICANT MODULATION IN THE HEPATIC HISTOLOGY

FIG. 2: HISTOPATHOLOGICAL FINDINGS IN THE KIDNEY. (A) CONTROL GROUP REVEALS NORMAL TISSUE ARCHITECTURE. (B) HGCL2 TREATED GROUP, NEPHROPATHIES ARE CHARACTERIZED BY CHRONIC TUBULE-INTERSTITIAL NEPHRITIS (C) HGCL2+ GA TREATED GROUP, THERE IS PRONOUNCED PRESERVATION OF TUBULAR INTERSTITIAL NEPHRITIS WITH MILD DECREASES IN THE DEGENERATIVE  (D) HGCL2+GG TREATED GROUP, SIGNIFICANT REDUCTION IN LESIONS WERE OBSERVED ONLY IN THE RATS THAT WERE CONTINUOUSLY TREATED WITH GG AFTER HG INTOXICATION

Fig. 2 H&E histopathological stain in the control group showed normal kidney morphology Fig. 2A, 2B showed the gross change of kidney was characterized by swelling, paleness of kidney, and congestion in HgCl₂ treated groups with chronic tubular interstitial nephritis, and many degenerated signs. Microscopic lesions with variable severity were noticed in the kidney. The lesions were characterized as various degrees of hemorrhage, necrobiotic changes, degenerative changes in tubular epithelium, hypercellularity of glomeruli, degeneration, and intratubular hemorrhage, with prominent nuclei as seen in Fig. 2B. Atrophic lining with intraluminal hyaline casts was also observed in GA treated group Fig. 2C. Meanwhile, GG administration after HgCl₂ showed mild mesangial hypercellularity in some of the glomeruli Fig. 2D. Dramatically, GA and GG treatment improved Hg nephrotoxicity, and less histological damage was observed in renal corpuscles and renal tubules.

DISCUSSION: Serum levels of total bilirubin, ALT, and AST are sensitive liver function indexes and are usually employed for the diagnosis of liver diseases. When serious liver damage occurs, these parameters are leaked out from hepatocytes into the blood. Moreover, the significant increase of serum urea and creatinine after exposure to HgCl₂ indicating its marked nephrotoxic effect and is assumed to be related to the fact that the kidney accumulates more mercury than other organs in the body with serious kidney damage caused these parameters to be elevated in serum. In the present study, liver and renal functions were detrimentally altered after HgCl₂ administration causing hepatorenal dysfunction evidenced by a significant elevation in total bilirubin, ALT and AST, enzyme activities, and urea, uric acid, and creatinine levels. Liver and kidney are the target metabolic and excretory organs for numerous harmful compounds and the major sites for Hg accumulation, which can alter their structure and function ¹⁸. The current results come in agreement with the previous work of Oriquat et al., ¹⁹ who revealed that HgCl₂ at a dose of 3.75 mg/kg body weight increased the AST and ALT, activities significantly than the control group. This study also indicates that mercury increases the levels of serum urea and creatinine; and decreases the iron level. Furthermore, Salman et al., ²⁰ who reported a significant increase in serum ALT, AST, creatinine, and urea levels in rats, received HgCl2 (0.5 mg/kg.BW) intraperitoneal daily for 2 weeks. Additionally, Abd Elghani et al., ²¹ observed a significant increase in serum values of ALT, AST, and GGT in the HgCl2 group. This could be attributed to severe damage in liver cells which releasing the hepatic enzyme into the serum. Treatment with GA and GG showed a marked improvement that was clear in the previously listed parameters, and these findings agreed with those of Nasir et al., 7 study who reveals several effects of GA treatment, which may delay the progression to renal failure in diabetic rats. Moreover, hung and suzuki, 22 reported that supplemental feeding with GG or PHGG might be effective for the prevention or management of adenine-induced chronic kidney disease symptoms in mice and attenuated the elevation of urea and creatinine levels. Also, Elblehi, et al., ²³ reported that GA may possess hepatoprotective effects ²⁸.

Since mercuric administration generates free radicals and subsequently increases oxidative stress, which leads to hepatotoxicity and accelerates nephrotoxicity, this adverse effect of HgCl₂ could be eliminated by GA and GG treatment probably because of their strong free radical scavenging activity through the electron donation pathway, protecting cells from oxidation and necrosis. Changes in oxidant-antioxidant balance, inhibition of antioxidant defense system, and enhanced production of reactive oxygen species (ROS) are considered to play a key role in Hg-induced toxicity ²⁴. Mercuric affects the cell physiology and integrity due to decreased GSH and GSH depending enzyme activity, leading to an increase of ROS such as superoxide anion radicals, hydrogen peroxide, and hydroxyl radicals, which stimulate lipid, protein, and DNA oxidation ²⁵. HgCl₂ administration initiates the formation of highly reactive substances such as ROS in addition to the stimulation of oxidative stress ²⁶ consequently, decreased the reduced glutathione level. This in turn led to cell degeneration, loss of membrane integrity, and cellular necrosis. These results come in accordance with Elblehi et al., ²³ who provoked a significant decrease in GSH and a significant increase in the level of malondialdehyde MDA were observed in hepatic and renal tissues of rats received HgCl₂ (5 mg/kg B.wt., intragastrical daily) for 30 days.

In the present study, we found that HgCl₂ significantly diminishes the level of GSH in kidney and liver tissues. Conversely, co-administration of GG with HgCl₂ showed a significant modulation in the level of GSH hepatorenal protective activity of GG was observed in the previous study ²⁷. This antitoxic effect of GA and GG could be attributed to the ability of their active components to reduce oxidative stress and preserve the structural integrity of hepatocellular and nephrotic cell membranes by the destruction of H₂O₂ and lipid hydroperoxides via elevating GSH and other antioxidants or direct scavenging activity against free radicals. Lui et al., ²⁸ partially hydrolyzed GG significantly elevated the activities of antioxidant enzymes and decreased the content of MDA in rat’s serum and brain tissue. Enhanced the activity of antioxidant enzymes and repaired the histopathological damage caused by free radicals.

Hydroxyproline is used for the estimation of the collagen content, considering that collagen contained 12.7% hydroxyproline by weigh ²⁹. Our results were parallel to those of Yadav et al., ³⁰ who concluded that renal and liver fibrosis is induced by HgCl₂, demonstrated by a significant elevation (p ≤ 0.05) of the hydroxyproline content in liver and kidney tissues compared to control. Whereas GA and GG treatment act as a rescue agent against the toxic effects of inorganic mercury when it is administered shortly after exposure to HgCl₂ indicated by alternation in Hydroxyproline content ³¹.

Our results reported a significant increase in both hepatic and renal TGFβ-1% in HgCl2-treated rats compared to normal control, as a result of mercuric toxicity induction including an increase in TGFβ-1 cytokine production cause collagen deposition. As confirmed by previous work of, Schon and Weiskirchen, ³² who reported a significant increase in hepatic and renal TGFβ-1% in HgCl₂-treated rats compared to control. Also, Gewin et al., ³³ reported that TGFβ^-1 signaling had been shown to alter numerous cellular processes in vitro that may be detrimental to the tubular response to chronic kidney diseases. TGFβ^-1 stimulates epithelial de-differentiation; thus, it may facilitate proximal tubule repair by accelerating de-differentiation of surviving epithelial cells, an important initial step in the repair ³⁴.  Moreover, Nabil et al., 1 observed that HgCl₂ without treatment showing a significant increase in serum AST, ALT, urea, creatinine, and uric acids compared to control. Furthermore, there was a significant reduction in the activity of the antioxidant enzymes and GSH in addition to a marked increase in the TGFβ-1% in kidney and liver tissues compared with the control group. There is now overwhelming evidence that the pro-fibrotic cytokine TGFβ-1 is a key mediator of progressive renal injury ³⁴. GA fermentation by colonic bacteria increases serum butyrate concentrations, so it is considered a prebiotic agent. GA has anti-inflammatory activity through its derivative butyrate ³⁵. GA had a favorable immune-modulator effect that was observed by previous work of Matsumoto et al., ³⁴ who revealed that treatment with GA, has a potential beneficial effect in renal disease by suppression of TGFβ-1 activity. Additionally, Hammad et al., ³⁶ showed that GA significantly attenuated the ureteric obstruction-induced increase in the tissue level of MDA and SOD and the rise in the gene expression of TNF-α and TGFβ^-1. Meanwhile, data from the current results reported that rats treated with GG showed a much more significant decrease in TGFβ-1%.

In the present study, we performed a histo-pathological examination to further support the biochemical evidence. We compared the morpho-logical structure among each group using H&E stain. HgCl₂ intoxication caused liver necrosis, swelling, and structure changes Fig. 1B in addition to renal tissue damage, collagen formation, and atrophy in the normal tubular architecture Fig. 2B. The liver is a major site of metabolism for mercury hence, severely affected by mercury. Previous studies also revealed that HgCl₂ caused histo-pathological and ultra-structural lesions evidenced by fatty degeneration and cell necrosis in the liver. The hepatic damage is usually observed as a rise in serum levels of liver enzymes such as ALT. Therefore, the elevation of these enzymes in serum may be attributed to their liberation from the cells into the circulation, indicating damage of the cell membrane or bile duct problems due to oxidative stress and the resulting lipid and protein oxidation ^{36, 38, 39}. Treatment with GA and GG significantly attenuated the pathological changes in both liver Fig. 1C & 1D and kidney Fig. 2C & 2D tissues as described by 4,30 in earlier studies that agreed with our results. Even though GG treatment showed much less histopathological changes than GA.

CONCLUSION: Finally, we conclude that GA and GG can ameliorate the toxic effect and retard the progression of hepatorenal fibrosis and tissue damage induced by HgCl₂. Moreover, GG exhibited more efficiency than GA.

ACKNOWLEDGEMENT: Nil

CONFLICTS OF INTEREST: All authors declare that there are no conflicts of interest.

REFERENCES:

1. Nabil A, Elshemy MM, Asem M and Gomaa HF: Protective Effect of DPPD on Mercury Chloride-Induced Hepatorenal Toxicity in Rats. Hindawi Journal of Toxicology 2020; 15(2020): 7.
2. Kim KH, Kabir E and Jahan SA: A review on the distribution of Hg in the environment and its human health impacts. Journal of Hazardous Materials. 2016, 306: 376-85.
3. Bridges CC and Zalups RK: Mechanisms involved in the transport of mercuric ions in target tissues. Archives of Toxicology.2017; 91(1): 63-81.
4. Zhang H, Tan X and Yang D: Dietary luteolin attenuates chronic liver injury induced by mercuric chloride via the rf2/NF κB/P53 signaling pathway in rats. Oncotarget 2017; 8(25): 40982-93.
5. Zulaikhah ST and Wibowo JW: The Effect of Tender Coconut Water on Free Radical Due to Mercury Exposure. International Journal of Public Health Science (IJPHS). 2018; 7(2): 102-06
6. Babiker R, Elmusharaf K and Keogh MB: Effect of Gum Arabic (Acacia Senegal) supplementation on visceral adiposity index (VAI) and blood pressure in patients with type 2 diabetes mellitus as indicators of cardiovascular disease (CVD): a randomized and placebo-controlled clinical trial. Lipids Health Dis. 2018; 17(1): 56.
7. Nasir O, Babiker S and Salim A: Protective effect of gum Arabic supplementation for type 2 diabetes mellitus and its complications. Int J Multidiscip Curr Res 2016; 4: 288-94.
8. Mudgil D, Barak S, Patel A and Shah N: Partially hydrolyzed guar gum as a potential prebiotic source. Int J Biol Macromol 2018; 112: 207-10.
9. Mirghani ME, Elnour AA and Kabbashi N: Determination of antioxidant activity of gum arabic: An exudation from two different locations. Sci Asia 2018; 44: 179-86.
10. Dowidar MF, Ahmed AI and Mohamed HR: Antidiabetic effect of pumpkin seeds and gum arabic and/or vildagliptin on type 2 induced diabetes in male rats. Int J Vet Sci 2020; 9(2): 229-33.
11. Anjum F, Gul S, Khan MI and Khan MA: Efficient synthesis of palladium nanoparticles using guar gum as stabilizer and their applications as catalyst in reduction reactions and degradation of azo dyes. Green Process Synth 2020; 9: 63-76.
12. ShiX, Ma H, Tong C, Qu M, Jin, Q and Li W: Hepato-protective effect of a polysaccharide from Crassostrea gigas on acute and chronic models of liver injury. Int J Biol Macromol 2015; 78: 142-48.
13. LiuY, Wang J, LiL, HuW, Qu Y, Ding Y, Meng L, Teng, L and Wang D: Hepatoprotective effects of Antrodia cinnamomea: The modulation of oxidative stress signaling in a mouse model of alcohol-induced acute liver injury. Oxid. Med. Cell Longev 2017; 2017: 784-23.
14. Sharma G, Sharma S, Kumar A, Al-muhtaseb AH, Naushad M and Ghfar AA: Guar gum and its composites as potential materials for diverseapplications: a review. Carbohydr Polym 2018; 199: 534-45.
15. Wu C, Liu J, Tang Y, Li Y, Yan Q and Jiang Z,: Hepato-protective Potential of Partially Hydrolyzed Guar Gum against Acute Alcohol-Induced Liver Injury in Vitro and Vivo. Nutrients 2019; 11(5): 963.
16. LiY, Yi P, Wang N, Liu J, Liu X, Yan Q and Jiang Z: High level expression of beta-mannanase (RmMan5A) in Pichia pastoris for partially hydrolyzed guar gum production. Int J Biol Macromol 2017; 105: 1171-79.
17. Levesque R, SPSS Programming and Data Management: A Guide for SPSS and SAS users. 3th Edition, United States of America 2007.
18. JoshiD, Mittal D, Shukla S, Srivastav A and Srivastav S: N-acetyl cysteine and selenium protects mercuric chloride-induced oxidative stress and antioxidant defense system in liver and kidney of rats: A histopathological approach. Trace Elem Med Biol 2014; 28: 218-26.
19. OriquatGA, Saleem TH, Naik RR, Moussa SZ and Al-Gindy MR: A sub-chronic toxicity study of mercuric chloride in the rat. Jordan Journal of Biological Sciences 2012; 141-46.
20. Salman M, Kotb A, Haridy M and Hammad S: Hepato- and nephroprotective effects of bradykinin potentiating factor from scorpion (Buthus occitanus) venom on mercuric chloride-treated rats. EXCLI. J 2016; 15: 807-16
21. Abd Elghani SA, Oda SS, Tohamy HG and Hashem MA: Hematological, biochemical and histopathological studies on the prophylactic effect of zinc sulphate against mercuric chloride toxicity in rats. Alexandria Journal of Veterinary Sciences 2020; 64(2): 102-09.
22. Hung TV and Suzuki T: Dietary fermentable fibers attenuate chronic kidney disease in mice by protecting the intestinal barrier. The Journal of Nutrition 2018; 148(4): 552-61.
23. Elblehi SS, Hafez MH, and El-Sayed YS: L-α-Phosphatidylcholine attenuates mercury-induced hepato-renal damage through suppressing oxidative stress and inflammation. Environmental Science and Pollution Research. 2019; 26(9): 9333-42.
24. Wildemann T, Siciliano S and Weber L: The mechanisms associated with the development of hypertension after exposure to lead, mercury species or their mixtures differs with metal and the mixture ratio. Toxicology 2016; 339: 1–8.
25. Abarikwu S, Benjamin S, Ebah S, Obilor G and Agbam G: Protective effect of Moringa oleifera oil against HgCl2-induced hepato- and nephro-toxicity in rats. J Basic Clin Physiol Pharmacol 2017; 28: 337-45.
26. Ahmad S and Mahmood R: “Mercury chloride toxicity in human erythrocytes: enhanced generation of ROS and RNS, hemoglobin oxidation, impaired antioxidant power, and inhibition of plasma membrane redox system,” Environmental Science and Pollution Research 2019; 26(6): 5645-57
27. Santas J, Espadaler J, Cune J and Rafecas M: Partially hydrolyzed guar gums reduce dietary fatty acid and sterol absorption in guinea pigs independent of viscosity. Lipids 2012; 47: 697-05.
28. Liu X, Wu C, Han D, Liu J, Liu H and Jiang Z: Partially hydrolyzed guar gum attenuates d-galactose-induced oxidative stress and restores gut microbiota in rats. Int J of Molecular Science 2019; 20(19): 4861-75.
29. Gow EKL, Kelly RM, Carmeliet DJP and Kitching RA: “Plasmin is not protective in experimental renal interstitial fibrosis1,” Kidney International 2004; 66(1): 68-76.
30. Yadav H, Sharma U, Singh S and Gupta Y: “Effect of Tribulus terrestris in mercuric chloride-induced renal accumulation of mercury and nephrotoxicity in rat,” Journal of Advanced Pharmaceutical Technology & Research 2019; 10(3): 132.
31. Iezzoni JC: “Diagnostic histochemistry in hepatic pathology,” Seminars in Diagnostic Pathol 2018; 381-89.
32. Schon HT and Weiskirchen R: “Immunomodulatory effects of transforming growth factor-β in the liver,” Hepatobiliary Surgery and Nutrition 2014; 3(6): 386-06.
33. Gewin L, Vadivelu S, Neelisetty S, Srichai MB, Paueksakon P, Pozzi,A, Harris RC and Zent R: Deleting the TGF-b Receptor Attenuates Acute Proximal Tubule Injury. J Am Soc Nephrol 2012; 23(12): 2001-11.
34. Matsumoto N, Riley S, Fraser D, Al-Assaf S, Ishimura E, Wolever T, Phillips GO and Phillips AO: Butyrate modulates TGF-b1 generation and function: Potential renal benefit for Acacia(sen) SUPERGUMTM (gum arabic)? Kidney International 2006; 69(2): 257-65.
35. Kamal E, Kaddam LA, Dahawi M, Osman M, Salih MA, Alagib A and Saeed A: Gum arabic fibers decreased inflammatory markers and disease severity score among rheumatoid arthritis patients, phase ii trial. International Journal of Rheumatology 2018; 2018: 1-6.
36. Hammad FT, Al Salam S, Nemmar A, Ali M and Lubbad L: The effect of Arabic gum on renal function in reversible unilateral ureteric obstruction. Biomolecules 2019; 9(25): 1-14.
37. El-Hussieny EA, Matoug MM and El-Sayed WM: The attenuation of mercuric chloride toxicity by flavonoids in male albino rats is independent on the number of hydroxyl groups on B-ring. Egyptian Journal of Zoology 2020; 73: 1-15.
38. Adams DH, Sonne C, Basu N, Dietz R, Nam DH, Leifsson PS and Jensen AL: Mercury contamination in spotted seatrout, Cynoscion nebulosus: an assessment of liver, kidney, blood, and nervous system health. Sci. Total Environ 2010; 408: 5808-16.
39. Abdel-Mejied EMM, Zahran AE, Omran FMM and Nabil A: “DPPD ameliorates renal fibrosis induced by HgCl₂ in rats,” Bioscience Research 2018; 15: 2416-25.
    

    ---

    How to cite this article:

    El-Rhman AA and Shosha NNH: Antitoxic effects of gum Arabic (Acacia senegal) and guar gum (Cyamopsis tetragonolobus) against hepatorenal toxicity induced by mercuric chloride in rats. Int J Pharm Sci & Res 2021; 12(12): 6353-61. doi: 10.13040/IJPSR.0975-8232. 12(12).6353-61.

    ---

    All © 2021 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.