Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice

Abstract

Cadmium (Cd) is an inessential trace metal that accumulates in the kidney and may lead to renal toxicity by mediating oxidative stress (OS), inflammatory reactions, and apoptosis. The main objective of this experiment was to inspect the protecting potential of taxifolin (TA) on Cd-induced renal toxicity. Adult male mice were allocated into equal five groups as follows: control, TA-treated (50 mg/kg, oral), CdCl2-treated (4 mg/kg body weight (BW), p.o.), pretreated with TA (25 mg/kg) 1 h before CdCl2 injection (4 mg/kg BW, p.o.), and pretreated with TA (50 mg/kg) 1 h before CdCl2 injection (4 mg/kg BW, p.o.) for 14 days. Cd-intoxicated mice revealed higher serum urea and creatinine levels and notable histopathological alterations in the renal tissues. Malondialdehyde (MDA), nitric oxide (NO), nuclear factor-kappa B (NF-κB) p65, tumor necrosis factor-α (TNF-α), and IL-1β were increased. In contrast, glutathione levels, catalase and superoxide dismutase activities, and IL-10 levels were decreased under Cd-administered effects. Conversely, the TA pre-treatment highly protected tissues from Cd-toxicity, improved renal function, decreased MDA and NO levels, attenuated inflammation, and improved redox status in the renal tissues of Cd-intoxicated mice. The TA pre-treatment of Cd-intoxicated mice showed down-regulation of both Bax and caspase-3 protein and up-regulation of Bcl-2 protein expression in the kidney. Furthermore, TA pre-treatment induced higher upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in kidney cells of Cd-intoxicated mice. Therefore, TA can protect renal tissues against Cd-induced nephrotoxicity via improving redox status, modulating inflammation, diminishing cell apoptosis, and activating the Nrf2/HO-1 signaling pathway.

Cardioprotective Effect of Taxifolin against Isoproterenol-Induced Cardiac Injury through Decreasing Oxidative Stress, Inflammation, and Cell Death, and Activating Nrf2/HO-1 in Mice

“…Moreover, TAX attenuated ISO-induced myocardial apoptosis, as indicated by the diminished Bax and caspase-3 and enhanced Bcl-2 expressions. Accordingly, TAX prevented cadmium-induced renal inflammation and apoptosis via the suppression of NF-κB, TNF-α, IL-1β, Bax, and caspase-3, and increased Bcl-2 expression [ 26 ]. Furthermore, TAX attenuated alcoholic liver disease in mice via mitigation of the NF-κB-enhanced inflammatory response and the regulation of Bax, Bcl-2, and caspase-3 expression in the liver [ 25 ].…”

“…In this study, treatment of ISO-intoxicated mice with TAX largely upregulated the Nrf2/HO-1 signaling pathway in the myocardium. In accordance, TAX protected against cadmium-induced oxidative tissue injury, inflammation, and apoptosis in the kidney [ 26 ], attenuated oxidative stress-induced cellular damage, and apoptosis in human RPE [ 24 ], and prevented lipopolysaccharide (LPS)-induced inflammatory injury in mice [ 67 ] by stimulating the Nrf2/HO-1 signaling pathway. Thus, the TAX-mediated Nrf2/HO-1 activation is attributed, at least in part, to its antioxidant and anti-inflammatory properties against ISO-induced cardiac injury.…”

“…The experiment included 30 Swiss albino mice (25–30 g), which were housed under standard conditions in an environment-controlled room and given free access to food and water. The vehicle solutions of physiological saline and 0.5% DMSO were used to dissolve ISO [ 12 ] and TAX [ 26 ], respectively.…”

“…The first group included the control mice which were given 0.5% DMSO for 14 days, using oral gavage, followed by two subcutaneous (s.c) injections of physiological saline on days 15 and 16; the second group (TAX) were given TAX (50 mg/kg) for 14 days followed by two 24-h interval sequential injections (s.c) of physiological saline; groups III (ISO), IV (TAX 25 mg/kg and ISO), and V (TAX 50 mg/kg and ISO) received oral 0.5% DMSO, 25 mg/kg TAX, or 50 mg/kg TAX, respectively, for 14 days before they were injected twice with ISO (100 mg/kg, s.c.) on the 15th and 16th days. The TAX and ISO dosages were chosen based on relevant articles by Algefare [ 26 ] and Abukhalil et al [ 11 ], respectively.…”

Effects of cadmium acetate contaminated drinking water on vital organs: A histopathological and biochemical study

“…As Cd dose and exposure time increased, uric acid and urea concentrations decreased (Figure 9A,B). [ 29,30 ] Serum creatinine levels increased as dose and exposure time increased (Figure 9C). Decrease in the serum glucose levels was observed with increasing dosage and exposure time [ 31 ] (Figure 9E).…”