Protective effect of Cyclotrichium niveum on gentamicin-induced nephrotoxicity in rats

Abstract

Gentamicin is an aminoglycoside antibiotic and has therapeutic importance in the treatment of Gram-negative aerobic bacterial infections. However, its clinical use is limited by nephrotoxicity, in which oxidative stress plays an important role. In this study, we investigated the protective effects of Cyclotrichium niveum, an endemic plant with antioxidant properties, against gentamicin-induced nephrotoxicity in rats. Renal injury and protection were assessed using blood urea nitrogen (BUN) and serum creatinine as markers of renal function, malondialdehyde (MDA) as a marker of oxidative stress, and histopathological evaluation of renal cortical injury. We first characterized the chemical composition of C. niveum essential oil (EO) by GC-MS, identifying pulegone as its major constituent (79.6%). Next, we evaluated the in vitro antioxidant activity of EO and isolated pulegone using the DPPH assay. Their protective effects were then examined in vivo at two dose levels each (EO, 200 and 400 mg/kg/day; pulegone, 50 and 100 mg/kg/day, p.o.) in rats receiving gentamicin (100 mg/kg/day, i.m.) for 8 days. Both EO and pulegone exhibited DPPH radical-scavenging activity. Gentamicin induced pronounced renal injury, whereas co-administration of either EO or pulegone provided protection, with more pronounced effects at the higher doses. In particular, gentamicin increased BUN and creatinine 2.74- and 2.37-fold, respectively (p < 0.001 for both), and produced grade 4–5 cortical injury in all histologically evaluated animals. At the higher doses, EO and pulegone reduced BUN by 56% and 64%, respectively (p = 0.042 and p < 0.001), and MDA by 57% and 55%, respectively (p = 0.006 for both). Pulegone additionally reduced creatinine by 39% (p = 0.041). Both treatments significantly improved histopathological injury grade (p = 0.002 and p = 0.008 for EO and pulegone, respectively). Together, these findings demonstrate that C. niveum EO and pulegone attenuate gentamicin-induced renal injury across functional, oxidative, and structural measures, with the strongest protection observed at the higher doses. Their in vitro antioxidant activity and attenuation of lipid peroxidation in vivo support an antioxidant contribution to the nephroprotective response, while the activity of isolated pulegone identifies it as an important bioactive contributor to the protective effects of C. niveum EO.