Rutin protects mercuric chloride-induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats

Objective: Mercury is a dangerous industrial and environmental pollutant which induces severe damage in diverse organs in animal and humans. The aim of this study was to investigate the protective effect of rutin (50 and 100 mg/kg body weight) against mercuric chloride (HgCl2) (1.23 mg/kg b.w.) toxicity in rats. Methods: The experiment was carried out in male Sprague Dawley rats (n = 35) which was divided into five groups as follow: control, rutin-100, HgCl2, HgCl2 + rutin-50 and HgCl2 + rutin-100. Results: The results showed that HgCl2 caused a marked increase in the malondialdehyde (MDA) level and significantly decreased antioxidant enzyme activities (p < 0.05). HgCl2 also provoked inflammatory responses by elevating the levels of tumor necrosis factor-alpha (TNF-alpha), B-cell lymphoma-3 (Bcl-3), interleukin-1 beta (IL-1 beta), nuclear factor kappa B (NF-kappa B), interleukin-33 (IL-33), and activities of mitogen-activated protein kinase 14 (MAPK 14) and myeloperoxidase (MPO) (p < 0.05). HgCl2 also prompted the apoptotic pathway by increasing the levels of Bcl-2 associated X protein (Bax) and p53, expression of terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) and cysteine aspartate specific protease-3 (caspase-3). HgCl2 changed histological integrity of kidney and expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) while caused a decrease in aquaporin 1 (AQP1) water channel protein level. In contrast to this, rutin significantly decreased oxidative stress, apoptosis, inflammation and histopathological alterations while increased AQP1 levels in kidney tissues (p < 0.05). Conclusion: The present study indicated that rutin has a nephroprotective effect due to its anti-inflammatory, antioxidant and antiapoptotic properties.