Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathways

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  FIGURE 1. Metabolites dereplicated from Saudi Tamarix honey.

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  FIGURE 2. Effect of STH on kidney functions. Effect of different doses of STH on (A) difference in body weight; (B) absolute kidney weight, (C) 24 h diuresis; (D) serum creatinine; and (E) BUN. a Significantly different from the control group; b significantly different from the cisplatin group; and c significantly different from the STH 50 mg/kg group, using one-way ANOVA followed by Tukey-Kramer multiple comparison test at p < 0.05 (n = 6). ANOVA: analysis of variance; BUN: blood urea nitrogen; SEM: standard error of the mean; STH: Saudi Tamarix honey.

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  FIGURE 3. Effect of STH on the renal redox status. Effect of different doses of STH on renal (A) MDA, (B) GSH, (C) SOD, and (D) TAC. a Significantly different from the Control group; b significantly different from the Cisplatin group; c significantly different from the STH 50 mg/kg group, using one-way ANOVA followed by the Tukey-Kramer multiple comparison test at p < 0.05 (n = 6); MDA: malondialdehyde; GSH: glutathione; SOD: superoxide dismutase; TAC: total antioxidant capacity.

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  FIGURE 4. Effect on the renal (A) TNF-α and (B) IL-6 levels. Effect of different doses of STH on the renal TNF-α and IL-6 level. a Significantly different from the Control group; b significantly different from the Cisplatin group; c significantly different from the STH 50 mg/kg group, using one-way ANOVA followed by Tukey-Kramer multiple comparison test at p < 0.05 (n = 6). TNF-α: tumor necrosis factor-alpha; IL-6: interleukin-6.

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  FIGURE 5. Photomicrographs of rat kidneys (H&E 200x). Effect of different doses of STH on renal histopathological changes. (A) A photomicrograph of a kidney section obtained from control rats; the section shows a normal renal architecture with normal corpuscles (black arrow) and convoluted tubules (red arrow); (B) a photomicrograph of kidney section obtained from CIS-treated (positive control) rats. The section displays bisected renal corpuscles (black arrow) and tubular congestion (yellow arrow) and interstitial edema and inflammations and immune cells infiltration (red arrow); (C) a photomicrograph of kidney section obtained from rats intoxicated with CIS and pre-treated with STH 50 mg/kg; the section shows a nearly normal structure of the kidney with normal renal corpuscles (black arrow), with most of the renal tubules being normal (red arrow) except for little interstitial hemorrhages (yellow arrows); (D) a photomicrograph of kidney section obtained from rats intoxicated with CIS and pre-treated with STH 100 mg/kg; the section shows a nearly normal structure of the kidney, with normal renal corpuscles (black arrows) and most of the renal tubules being normal (red arrow), except for…

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  FIGURE 6. Effect of STH on renal STAT3, Nrf2, and caspase-3 protein expression. (A) Western blot analysis of kidneys from the normal group and the CIS group with or without STH using STAT3, Nrf2, and caspase-3 Abs together with β-Actin Ab as an internal control (n = 6). Quantitative analysis (fold changes) of western blots depicted effect of different doses of STH on (B) STAT3, (C) Nrf2, and (D) caspase-3 protein expression in graphs using ImageJ/NIH software. a Significantly different from the control group; b significantly different from the cisplatin group; c significantly different from the STH 50 mg/kg group using one-way ANOVA followed by Tukey-Kramer multiple comparison test at p < 0.05 (n = 6).