Bstances may potentially have deleterious effects (pro-oxidation action), particularly when precise modulation of ROS levels

Bstances may potentially have deleterious effects (pro-oxidation action), particularly when precise modulation of ROS levels are necessary for normal cell function. The fact that antioxidants may exhibit pro-oxidant activity depending on dosage and presence of free transition metals at cellular sites [33-35], and appearance of the toxicity with HMR-1275 web higher dose does not totally exclude the contribution of flavonoids.Morphologic pathologyto kidney damage, as it was shown to cause mild-tomoderate injury in the histopathologic evaluation, but it could also be ascribed to khat-induced delay in intestinal absorption that contributes to some degree of malnutrition [38-40] or increased plasma leptin level that leads to loss of appetite [41]. Kidney weight gain probably explained by the edema that was caused by gentamicin and khat induced acute tubular necrosis [19]. The histopathological results were paralleled by serum, antioxidant and lipid peroxidation findings. Rats treated with gentamicin revealed extensive and marked renal tubular necrosis. Although khat alone was not able to produce extensive kidney damage, it resulted in a wideranging damage that even included the epithelial cells when combined with gentamicin. This histopathological evidence once again clearly reaffirms the direct nephrotoxic potential of khat. Although the mechanism by which khat produces nephrotoxicity is not clearly known, it is thought to result from local decrease in blood supply, possibly from narrowing of the renal arteries [24,42].Conclusions Administration of khat at higher dose (400 mg/kg) was shown to cause renal damage. Moreover, gentamicininduced disturbance in renal indices were considerably accentuated by high dose of crude khat extract. Khat, alone or with gentamicin was also found to alter renal histopathology, normalized kidney weight and body weight of rats. Thus, the data collectively indicate that khat does not play a permissive role but has a direct nephrotoxic potential, albeit to a small extent, that creates synergism when combined with other nephrotoxic agents such as gentamicin. The use of khat at higher dose may cause oxidative stress by depleting anti-oxidative mechanisms or by enhancing pro-oxidant components of tissues, leading to renal injury. More reasonably, khat seems to be able to perturb the delicate balance between protective and damaging mechanisms of a cell that is required for optimal activity, thereby producing oxidative damage.Competing interests The authors declare that they have no competing interest. Authors’ contributions All authors involved in the design and write up of the study, and ZS conducted the actual study and the statistical analysis. Both authors approved the submitted version of the manuscript. Acknowledgement The authors are thankful to Addis Ababa University for the financial support. Received: 1 October 2013 Accepted: 18 February 2014 Published: 20 February 2014 References 1. Patel NB: Mechanism of action of cathinone: the active ingredient of khat (Catha edulis). East Afr Med J 2000, 77:329?32.K200 and K400 rats showed a significant body weight loss compared to controls, although the extent PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27362935 of loss was lower than gentamicin. Gentamicin-induced weight loss could be associated with direct renal tubular injury. Injury of the renal tubules leads to subsequent loss of tubular cells that take part in renal water reabsorption. This is accompanied by loss of water, leading to dehydration and loss of body weight [36]. O.