Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice
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 toxi...
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MDPI AG
2022-07-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/8/1150 |
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| author | Abdulmohsen I. Algefare |
| author_facet | Abdulmohsen I. Algefare |
| author_sort | Abdulmohsen I. Algefare |
| collection | DOAJ |
| description | 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), CdCl<sub>2</sub>-treated (4 mg/kg body weight (BW), p.o.), pretreated with TA (25 mg/kg) 1 h before CdCl<sub>2</sub> injection (4 mg/kg BW, p.o.), and pretreated with TA (50 mg/kg) 1 h before CdCl<sub>2</sub> 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. |
| first_indexed | 2024-03-09T04:12:34Z |
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| language | English |
| last_indexed | 2024-03-09T04:12:34Z |
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| record_format | Article |
| series | Life |
| spelling | doaj.art-3ef6c88c59244e0a922e2e84cb19819b2023-12-03T13:58:34ZengMDPI AGLife2075-17292022-07-01128115010.3390/life12081150Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in MiceAbdulmohsen I. Algefare0Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaCadmium (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), CdCl<sub>2</sub>-treated (4 mg/kg body weight (BW), p.o.), pretreated with TA (25 mg/kg) 1 h before CdCl<sub>2</sub> injection (4 mg/kg BW, p.o.), and pretreated with TA (50 mg/kg) 1 h before CdCl<sub>2</sub> 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.https://www.mdpi.com/2075-1729/12/8/1150TAcadmiumnephrotoxicityNrf2apoptosisantioxidants |
| spellingShingle | Abdulmohsen I. Algefare Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice Life TA cadmium nephrotoxicity Nrf2 apoptosis antioxidants |
| title | Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice |
| title_full | Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice |
| title_fullStr | Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice |
| title_full_unstemmed | Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice |
| title_short | Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice |
| title_sort | renoprotective and oxidative stress modulating effects of taxifolin against cadmium induced nephrotoxicity in mice |
| topic | TA cadmium nephrotoxicity Nrf2 apoptosis antioxidants |
| url | https://www.mdpi.com/2075-1729/12/8/1150 |
| work_keys_str_mv | AT abdulmohsenialgefare renoprotectiveandoxidativestressmodulatingeffectsoftaxifolinagainstcadmiuminducednephrotoxicityinmice |