Vitamin U has a protective effect on valproic acid-induced renal damage due to its anti-oxidant, anti-inflammatory, and anti-fibrotic properties

Abstract

The aim of present study was to investigate the effect of vitamin U (vit U, S-methylmethionine) on oxidative stress, inflammation, and fibrosis within the context of valproic acid (VPA)-induced renal damage. In this study, female Sprague Dawley rats were randomly divided into four groups: Group I consisted of intact animals, group II was given vit U (50 mg/kg/day, by gavage), group III was given VPA (500 mg/kg/day, intraperitonally), and group IV was given VPA + vit U. The animals were treated by vit U 1 h prior to treatment with VPA every day for 15 days. The following results were obtained in vit U + VPA-treated rats: (i) the protective effect of vit U on renal damage was shown by a significant decrease in histopathological changes and an increase in Na(+)/K(+)-ATPase activity; (ii) anti-oxidant property of vit U was demonstrated by a decrease in malondialdehyde levels and xanthine oxidase activity and an increase in glutathione levels, catalase and superoxide dismutase activities; (iii) anti-inflammatory property of vit U was demonstrated by a decrease in tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1 levels, and adenosine deaminase activity; (iv) anti-fibrotic effect of vit U was shown by a decrease in transforming growth factor-β, collagen-1 levels, and arginase activity. Collectively, these data show that VPA is a promoter of inflammation, oxidative stress, and fibrosis which resulted in renal damage. Vit U can be proposed as a potential candidate for preventing renal damage which arose during the therapeutic usage of VPA.

Study on the influence of caffeic acid against sodium valproate–induced nephrotoxicity in rats

“…High levels of ROS are associated with inflammation, and in a reciprocal manner cytokines stimulate ROS generation, also accompanied by the increase in TGF‐β as reported by Gezginci‐Oktayoglu et al. . TGF‐β leads to Notch activation and apoptosis via inducing p53.…”

“…In the SVP group, rats received SVP (500 mg/kg/day i.p. for 2 weeks). In the CAFF group, rats received CAFF (50 mg/kg/day p.o.…”

“…Cases of serious renal damage as interstitial nephritis and proximal renal tubule dysfunction have been observed with SVP therapy. According to several published articles, reactive oxygen species (ROS) are the main mediator of SVP toxicity, where SVP‐induced ROS generation has been observed in cases of renal toxicity , hepatotoxicity , neurotoxicity, and also in teratogenicity. …”

Mechanism of valproic acid‐induced Fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney

“…Although the effect of VPA on the biochemical markers of kidney injury doesn't seem to be dose‐dependent, several biochemical parameters were significantly higher in VPA 500 mg/kg treated group in comparison with VPA 250 mg/kg (Table ). Previous investigations also mentioned 500 mg/kg of VPA as the nephrotoxic dose of this drug …”

“…Hepatotoxicity, hyperammonaemic encephalopathy, hypersensitivity reactions, weight gain, pancreatitis, haematological abnormalities, gastrointestinal disturbances, neurological toxicity, as well as renal injury, have been reported after VPA administration . Several investigations indicated the injurious effect of VPA on the kidney in human and animal models . There is no clear mechanism for VPA‐induced renal injury.…”