Renoprotective effects of cinnamon oil against APAP-Induced nephrotoxicity by ameliorating oxidative stress, apoptosis and inflammation in rats

Abstract

Acetaminophen (APAP) is used as a primary medication in relieving moderate pain and fever. However, APAP is associated with toxic effects in renal tissue that appear because of its free radicals property. The principle goal of the present work is to assess the kidney damage by APAP and its restore antioxidative property of cinnamon oil (CO). Animals were distributed into six animals each in six groups. Rats were administered with three varying doses of CO from 50 to 200 mg/kg b.w. respectively and only a single dose of APAP. APAP induced an alteration in serum biochemical markers, imbalance in oxidative parameters, morphological changes in kidney tissue along with increased interleukins cytokines (IL-1β & 6) and caspase (3, 9) levels. CO administration significantly ameliorates all the parameters and histopathological changes were restored. Moreover, it also restored the activities of antioxidative enzymes. Our work proved that an variance of oxidative markers in the kidney by APAP is ameliorated by CO in rats. Thus, CO could be used in reducing APAP-induced nephrotoxicity.

Keywords: Acetaminophen; Caspases-3, 9; Cinnamon oil; Inflammation; Nephrotoxicity; Oxidative stress.

Fig. 1

Effect of CO on kidney tissue levels of LPO in nephrotoxicity induced by APAP. Data presented as Mean ± SEM (n = 6). ***p < 0.001 designates significant difference between only APAP with control group, ^##p < 0.01 and ^#p < 0.05 shows significant difference from APAP untreated group (VEH).

Fig. 2 and 3

CO attenuates APAP induced activation of inflammatory mediators IL-1β (3) and IL-6 (4) in the kidneys of rats treated with APAP. ELISA results are presented as group Mean ± SEM (n = 6). ***p < 0.001 compared to control group; ^#p < 0.05 ^##p < 0.01and ^###p < 0.001, respectively, compared to the APAP group.

Fig. 4 and 5

CO attenuated activation of caspase-3 (5) and caspase-9 (6) in kidney tissue of rats treated with APAP. Data presented as Mean ± SEM (n = 6). **p < 0.01 designates significant difference between only APAP from control group, ^#p < 0.05 and ^##p < 0.01 shows significant difference from APAP untreated group (VEH).

Fig. 6

Effect of CO on morphological changes in APAP treatment rat using H&E staining in the kidney of control, APAP and different doses of APAP + CO groups. Kidneys from the control group (A) showed no histological changes. Pathological alteration included infiltrating cells and tubular necrosis (arrowhead), epithelial degeneration (arrow), tubular dilatation (star), and swelling in APAP treated rats (B). Histological damages were ameliorated in kidneys from rats treated with CO in APAP + CO (C, D and E) when compared with kidneys in rats treated with APAP alone. Values are expressed in means ± S.E.M. (n = 6). ***P < 0.001 APAP vs. control group; ^#P < 0.05, ^##P < 0.01 APAP + CO vs. APAP alone-treated group.