Immunosuppressant drug tacrolimus induced mitochondrial nephrotoxicity, modified PCNA and Bcl-2 expression attenuated by L. in CD1 mice.

Tacrolimus (TAC) is used sporadically as an immunosuppressive agent for organ transplantation, but its clinical used is limited due to its marked nephrotoxicity. L. (Lamiaceae) (OB) had been shown to possess antioxidant, anti-inflammatory and nephroprotective activity, and effective at improving renal inflammation and glomerular. In our study, we aim to evaluate the efficacy of the OB against TAC-induced mitochondrial nephrotoxicity in CD1 mice. Mice were randomly divided into four groups. Group 1 (control group); administered orally with normal saline (1 mL/kg) for two weeks; Group 2 (OB extract treated-group) (500 mg/kg b.wt) gavaged once/day for two weeks; Group 3 (TAC-treated group) (3 mg/kg b.wt, administered ip once a day for two weeks); and Group 4; (TAC plus OB extract treated-group). Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. The OB extract was high in phenolic content (50.3 mg/g of gallic acid equivalent), total flavonoids (14.5 mg/g CE equivalent). The potential antioxidant efficacy of the extract (IC) was 24.5 μg/mL. OB pretreatment significantly improved the TAC-induced changes in biochemical markers of nephrotoxicity for instance blood urea nitrogen (BUN), creatinine, total protein, and albumin (P < 0.01, when compared with TAC treated group). Also, it significantly restored the increase activities of TBARS, protein carbonyl (PC) (P < 0.001, when compared to healthy control group) and decreased activities of nonprotein thiol (NP-SH) levels, Mn-superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPx) antioxidants of mitochondria. The nephroprotective efficacy of the OB leaves extract was further evident by histopathological analysis together with the PCNA-ir and Bcl2. The upshot of the present study revealed that the OB possessed significant antioxidant and nephroprotective activity and had a preventive effect on the biochemical alterations and histological changes in TAC-treated mice.