Galangin Attenuates Liver Injury, Oxidative Stress and Inflammation, and Upregulates Nrf2/HO-1 Signaling in Streptozotocin-Induced Diabetic Rats

Al-Amarat, Wesam; Abukhalil, Mohammad H.; Althunibat, Osama Y.; Alfwuaires, Manal; Alnamshan, Mashael M.; Alqosaibi, Amany I.; Ahmeda, Ahmad; Kamel, Emadeldin M.; Arab, Hany H.; Mahmoud, Ayman M.

doi:10.3390/pr9091562

Cited by 19 publications

(9 citation statements)

References 75 publications

(98 reference statements)

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“…In this study, CP suppressed hepatic Nrf2/HO-1 signaling as evidenced by the decreased mRNA abundance of Nrf2, NQO-1, and HO-1, Nrf2 protein, and HO-1 activity, demonstrating the surplus production of ROS. Although activated by ROS under physiological conditions, Nrf2 downregulation has been reported under conditions of excessive and prolonged ROS, including CP hepatotoxicity [ 30 , 31 , 41 , 42 , 43 , 44 ]. API upregulated hepatic Nrf2/HO-1 signaling in CP-intoxicated rats as shown by the upregulated Nrf2, NQO-1, and HO-1, which explained the enhanced antioxidant enzymes.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Nrf2/HO-1 Signaling and Attenuation of Oxidative Stress, Inflammation, and Cell Death Mediate the Protective Effect of Apigenin against Cyclophosphamide Hepatotoxicity

et al. 2022

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Liver injury is among the adverse effects of the chemotherapeutic agent cyclophosphamide (CP). This study investigated the protective role of the flavone apigenin (API) against CP-induced liver damage, pointing to the involvement of Nrf2/HO-1 signaling. Rats were treated with API (20 and 40 mg/kg) for 15 days and received CP (150 mg/kg) on day 16. CP caused liver damage manifested by an elevation of transaminases, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), and histological alterations, including granular vacuolation, mononuclear cell infiltration, and hydropic changes. Hepatic reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) were increased and glutathione (GSH) and antioxidant enzymes were decreased in CP-administered rats. CP upregulated the inflammatory markers NF-κB p65, TNF-α, IL-6, and iNOS, along with the pro-apoptotic Bax and caspase-3. Pre-treatment with API ameliorated circulating transaminases, ALP, and LDH, and prevented histopathological changes in CP-intoxicated rats. API suppressed ROS, MDA, NO, NF-κB p65, iNOS, inflammatory cytokines, oxidative DNA damage, Bax, and caspase-3 in CP-intoxicated rats. In addition, API enhanced hepatic antioxidants and Bcl-2 and boosted the Nrf2 and HO-1 mRNA abundance and protein. In conclusion, API is effective in preventing CP hepatotoxicity by attenuating oxidative stress, the inflammatory response, and apoptosis. The hepatoprotective efficacy of API was associated with the upregulation of Nrf2/HO-1 signaling.

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Section: Discussionmentioning

confidence: 99%

Upregulation of Nrf2/HO-1 Signaling and Attenuation of Oxidative Stress, Inflammation, and Cell Death Mediate the Protective Effect of Apigenin against Cyclophosphamide Hepatotoxicity

et al. 2022

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“…In this study, Cd suppressed renal Nrf2/HO-1 signaling as evidenced by the lowered Nrf2 and HO-1 levels in the kidney, demonstrating the surplus production of ROS. Although activated by ROS under physiological conditions, Nrf2 downregulation has been reported under conditions of excessive and prolonged ROS [ 31 , 58 , 59 , 60 ]. Extensive evidence indicates that various naturally occurring compound-mediated Nrf2 activation can protect against drugs/chemicals-induced renal injury [ 58 , 59 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

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

Algefare

2022

Life

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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.

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“…ELISA kits (R&D Systems, USA) were employed to determine interleukin 1 beta (IL-1 β), IL-6, and tumor necrosis factor-alpha (TNF-α) levels in the kidney homogenate as described previously ( Al-Amarat et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Formononetin Ameliorates Renal Dysfunction, Oxidative Stress, Inflammation, and Apoptosis and Upregulates Nrf2/HO-1 Signaling in a Rat Model of Gentamicin-Induced Nephrotoxicity

et al. 2022

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Gentamicin (GEN) is a bactericidal aminoglycoside known to cause nephrotoxicity. Formononetin (FN) is a potent flavonoid that exhibits numerous promising pharmacological activities. In this study, we have assessed the nephroprotective efficacy of FN against GEN-induced renal injury in rats. Rats were orally administered with FN (60 mg/kg/day, for 2 weeks) and were co-treated with intraperitoneal (i.p.) injection of GEN (100 mg/kg/day) during the days 8–14. GEN-treated rats demonstrated increased urea and creatinine levels in serum associated with marked histopathological changes in the kidney. Malondialdehyde (MDA) and protein carbonyl contents were elevated, whereas glutathione concentration and catalase and superoxide dismutase activities were lowered in GEN-administered rats. The FN largely prevented tissue damage, attenuated renal function, reduced MDA and protein carbonyl, and enhanced antioxidant capacity in the kidney of GEN-administrated animals. The kidney of GEN-treated rats demonstrated elevated Bax and caspase-3 protein expression, accompanied by lowered Bcl-2 protein expression, an effect that FN attenuated. Moreover, FN treatment caused upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in renal tissue of GEN-intoxicated animals. Collectively, FN protects against GEN-caused renal damage via exhibiting antioxidant, anti-inflammatory, and antiapoptotic activities and augmenting Nrf2 signaling, suggesting FN as a promising agent for preventing drug-induced organ damage.

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Galangin Attenuates Liver Injury, Oxidative Stress and Inflammation, and Upregulates Nrf2/HO-1 Signaling in Streptozotocin-Induced Diabetic Rats

Cited by 19 publications

References 75 publications

Upregulation of Nrf2/HO-1 Signaling and Attenuation of Oxidative Stress, Inflammation, and Cell Death Mediate the Protective Effect of Apigenin against Cyclophosphamide Hepatotoxicity

Upregulation of Nrf2/HO-1 Signaling and Attenuation of Oxidative Stress, Inflammation, and Cell Death Mediate the Protective Effect of Apigenin against Cyclophosphamide Hepatotoxicity

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

Formononetin Ameliorates Renal Dysfunction, Oxidative Stress, Inflammation, and Apoptosis and Upregulates Nrf2/HO-1 Signaling in a Rat Model of Gentamicin-Induced Nephrotoxicity

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