Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

Abstract

Exposure to cadmium (Cd) has harmful effects on the liver and kidney. Resveratrol (RES) is an herbal substance that functions as a protective mediator. This study aimed to investigate the effects of RES on the histology of liver and kidney in Cd-exposed mice. Male mice were divided into 4 groups daily receiving normal saline (1 mL normal saline/d), Cd (1 mg/kg/d), RES (20 mg/kg/d), and Cd plus RES, respectively. After 4 weeks, the liver and kidney components were evaluated using stereological methods. The total volume and number of hepatocytes, and volume of fibrous tissue were respectively increased by 34%, 58%, and a 3-fold in the Cd-exposed mice in comparison to the control animals (P＜0.03). On the other hand, the volume of the main vasculature (sinusoids and central veins) was decreased by 36% in the Cd group compared to the control mice (P＜0.03). Considering the kidney, the results showed a 3-fold increase in the total glomeruli volume and a 7-fold increase in fibrous tissue in the Cd-treated group compared to the control mice (P＜0.03). After Cd treatment, a 32% reduction was observed in the volume and length of the proximal and distal convoluted tubules. RES-treatment alone did not induce any structural changes. In comparison to the Cd group, an increase in the normal components of the liver and kidney and a decrease in the formation of the fibrous and degenerated tissues were observed in the Cd+RES-treated mice (P＜0.03).

Flavocoxid, a Natural Antioxidant, Protects Mouse Kidney from Cadmium‐Induced Toxicity

“…Therefore, the increased MMP-9 levels could be responsible for tissue collagen-reduced stain at the basement membrane level of both glomeruli and tubules demonstrated with SR stain. These morphological data seem to be in contrast with previous results from a stereological study on mouse kidney exposed for four weeks to CdCl 2 [ 19 ], where an increased volume of the fibrous tissue was observed in HE-stained specimens compared to controls. The differences could be related to the longer time of exposure to Cd in the work of Rafati et al [ 19 ], which could have induced a more serious hypoxia with increase in fibrosis [ 64 ].…”

“…The proximal tubular epithelium, owing to its active role in reabsorption, is particularly sensitive to damage by oxidative stress, so that a possible link between Cd toxicity and renal cell injury was described [ 24 ]. However, Cd-induced structural changes of the glomeruli, consisting in increased mesangial matrix and glomerular swelling with wider urinary space, were also described [ 18 , 19 ].…”

“…Several protective agents were found effective in defending against Cd-induced nephrotoxicity [ 9 , 16 , 19 , 52 – 55 ].…”

“…In particular, it was demonstrated that the target sites of Cd are the proximal tubules [ 12 ]; in these structures, lesions of the brush border and fragmentation of the epithelial cells with the granular cytoplasm were observed [ 13 – 17 ]. However, Cd-induced structural damages of the glomeruli [ 18 ], consisting in increased mesangial matrix, glomerular swelling, and increased urinary space, were also demonstrated [ 19 ].…”

Endoplasmic reticulum stress eIF2α–ATF4 pathway-mediated cyclooxygenase-2 induction regulates cadmium-induced autophagy in kidney

“…28 Our study showed that Cd exposure resulted in hepatomegaly, which was consistent with previous studies. 29, 30 mMTs mRNA was induced by Cd both in livers and kidneys, which indicated that Cd had been transferred and released into the kidney which might result in renal damage. In line with these data, histological analysis showed glomerular shrinkage and tubular degeneration upon Cd exposure.…”