Protective Effect of DPPD on Mercury Chloride-Induced Hepatorenal Toxicity in Rats

Abstract

Mercury is a global environmental pollutant, accumulating mainly in the kidney and liver inducing hepatorenal toxicity, oxidative stress, and tissue damage. Oxidative stress is caused by an imbalance between free radicals' production and cellular antioxidant defense systems. In the present study, we investigated the effect of N N'-diphenyl-1, 4-phenylenediamine (DPPD) antioxidant activity against mercury chloride- (HgCl₂-) induced renal and hepatic toxicity. Thirty adult female Sprague Dawley rats were divided into three equal groups: the first group was injected with saline only and served as a control, the second group was injected with HgCl₂, and the third group received DPPD + HgCl₂ rats injected with HgCl₂ without treatment showing a significant increase in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, and uric acids compared to control. Moreover, the second group showed a significant reduction in the activity of the antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH)) in addition to a marked increase in the malondialdehyde (MDA) content, histopathological alterations, collagen deposition, CD8%, CD4%, and TGF-β% in kidney and liver tissues compared with the control group. Treatment with DPPD showed significant recovery (p ≤ 0.001) in all previous parameters and histopathological examination. In conclusion, we suggested that DPPD may have a promising antioxidant capacity, gives it the applicability to be used as a prophylactic agent against mercury-induced hepatorenal cytotoxicity in the future.

Figure 1

H&E-stained and Masson-stained kidney tissues of rats from different groups (magnification ×200). (a) Section of the control group showing the normal architecture of the kidney. (b) Significant increase in tubular dilatation and degenerative changes observed in HgCl₂-injured rats. (c) Treatment with DPPD significantly attenuated the renal histopathological changes. (d) Masson's trichrome staining indicated no abnormal collagen in the control group. (e) Sections of HgCl₂-treated group indicated an increase in fibrosis stained in blue. (f) Kidney section of rats cotreated with HgCl₂ + DPPD showed a significant decrease in collagen deposits. (g) Pathological scoring showed a significant increase in the tubular injury score in the HgCl₂-treated group when compared with other groups. (h) Comparison between different groups in the Masson% area. Data were mean ± SD. ^∗p < 0.01 vs. control; ^#p < 0.01 vs. HgCl₂.

Figure 2

H&E-stained and Masson-stained liver tissues of rats from different groups (magnification ×200). (a) Hepatic histology of the control group, showing normal hepatic lobular architecture. (b) Hepatic degenerative changes with extensive cell necrosis observed in HgCl₂-injured rats. (c) Rats treated with DPPD showed a significant modulation in the hepatic histology towards normal. (d) Control group stained with Masson's trichrome showed that the natural structure and collagen fibers cannot be seen. (e) Accumulation and progression of collagen fibers in the liver of the HgCl₂ group. (f) Significant decrease in collagen fibers observed in rats cotreated with HgCl₂ + DPPD. (g) Pathological scoring showed a significant increase in the hepatic injury score in the HgCl₂-treated group compared with other groups. (h) Comparison between different groups in the Masson% area. Data were mean ± SD. ^∗p < 0.01 vs. control; ^#p < 0.01 vs. HgCl₂.