Ameliorative effect of sesamin in cisplatin-induced nephrotoxicity in rats by suppressing inflammation, oxidative/nitrosative stress, and cellular damage

Abstract

Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.

Fig. 1

The plasma concentration of tumor necrosis factor (TNF-α), interleukin (IL-1β), transforming growth factor (TGF-β1), cystatin C, renalase, and the renal activity of myeloperoxidase (MPO) in control rats, and rats treated with cisplatin or sesamin (separately or in combi-nation). Each column and vertical bar represents mean ± SEM (n=6). Differences between the groups were assessed by one-way analysis of variance (ANOVA) followed by Bonferroni’s multiple comparison test.

Fig. 2

The renal concentration or activity of superoxide dismutase (SOD), catalase (CAT), glutathione re-ductase (GR), total antioxidant capa-city (TAC), malondialdehyde (MDA), and nuclear factor erythroid 2-related factor 2 (Nrf2) in control rats, and rats treated with cisplatin or sesamin (separately or in combination). Each column and vertical bar represents mean ± SEM (n=6). Differences between the groups were assessed by one-way analysis of variance (ANOVA) followed by Bonferroni’s multiple comparison test.

Fig. 3

The renal concentration of total nitric oxide (NO), nitrite and nitrate, and the nitrate/nitrite ratio in control rats, and rats treated with cisplatin or sesamin (separately or in combination). Each column and vertical bar represents mean ± SEM (n=6). Differences between the groups were assessed by one-way analysis of variance (ANOVA) followed by Bonferroni’s multiple comparison test.

Fig. 4

Representative micrographs of kidney sections from control rats, and rats treated with cisplatin or sesamin (separately or in combination), stained with hematoxylin and eosin (H & E). The control (A and B) and sesamin-treated group (E and F) show normal kidney architecture and histology. The cisplatin-treated group (C and D) shows acute tubular necrosis in 52±3.62 % of examined tissue areas (thin arrows) with tubular distention with necrotic material. The (cisplatin + sesamin)-treated group (G and H) shows dramatic improvement in the histologic appearance with absence of acute tubular necrosis and complete recovery of injured tubules.