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Background: some data suggest the protective effect of portulaca oleracea against renal failure and its association with the preservation of the renal antioxidant status and the regulation of apoptosis. objectives: the current study aimed to examine the renoprotective effects of treatment with portulaca oleracea (po), a prominent hydrogen sulfide donor, in a 5/6 nephrectomy animal model. methods: in this experimental study, 32 adult male wistar rats, initially weighting 200 - 250 g, were housed under standard conditions since the beginning of april 2017 until the end of january 2018. the effect of po extract on renal dysfunction induced by gentamicin was studied. the male rats were treated with two selected doses of po (i.e., 200 and 600 mg/kg p.o.) and normal saline (5 ml/kg p.o.) for 28 consecutive days. gentamicin (80 mg/kg/day intraperitoneally [i.p.]) was administered to two groups for seven days, and they were considered as the po200 and po600 gentamicin groups, respectively, while the group administered normal saline (5 ml/kg p.o.) for 35 consecutive days was considered as the control group. the rats were anesthetized on day 36. then, they were sacrificed under deep anesthesia, and plasma and tissue samples were obtained. results: treatment with po decreased the renal histological damages and apoptosis induced by gentamicin and enhanced renal function parameters compared to the gentamicin group. conclusions: the present findings provide strong evidence to support the traditional medicinal use of this herb by the tribal people in the treatment of renal impairment. finally, these results support the therapeutic effect of po in preventing the development of renal dysfunction.