Non-Neuronal Pathology of Rotenone in Sprague Dawley Rats: Potential Protective Effect of Lithium Chloride

Abstract

Rotenone (ROT), a mitochondrial complex I inhibitor, has been linked to Parkinson’s disease (PD) since Betarbet and her colleagues reproduced the most features of the disease in a murine model challenged with ROT in 2000. Since that time, ROT is extensively used to model PD and there are no detailed reports investigating its adverse effects on non-neuronal tissues. Accordingly, our current study tried to investigate non-neuronal pathology of ROT in rats. Besides, potential protective effect of lithium chloride (LiCl) against ROT-induced pathology was investigated. In which, forty male Sprague Dawley (SD) rats were assigned into 4 groups; vehicle-, ROT-, ROT and LiCl- and LiCl-treated groups. ROT (2 mg/kg b.w.) and LiCl (60 mg/kg b.w.) were respectively administered subcutaneously and orally, five times a week for 5 weeks. At the end of each treatment, animals’ body weight and gastrointestinal functions were assessed. Blood samples and tissue specimens from liver, kidney, stomach, adrenal gland and testis were obtained, and adopted for biochemical and hsitopathological analysis, respectively. ROT resulted in gastrointestinal dysfunction, decreased the activity of some antioxidant enzymes and increased MDA levels. Histopathologically, ROT characteristically injured blood vasculature in different body organs and consequently damaged the parenchyma of these organs. Co-treatment of rats with ROT and LiCl alleviated most adverse effects that produced by ROT. In conclusion, ROT adversely affects non-neuronal organs in rats, most notably liver, kidney, stomach, adrenal gland and testis. Against ROT, LiCl has the potential to provide observable protection against ROT-induced damage in these organs.