Regulation of renal nitric oxide and eNOS/iNOS expression by tadalafil participates in the mitigation of amphotericin B–induced renal injury: Down-regulation of NF-κB/iNOS/caspase-3 signaling

Abdel-Rahman, Doaa M.; Messiha, Basim Anwar Shehata; Ali, Fares E.M.; Azouz, Amany A.

doi:10.1007/s00210-023-02787-w

Cited by 3 publications

(1 citation statement)

References 66 publications

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“…Additionally, ATO administration markedly reduced eNOS levels, indicating increased vasoconstriction, consistent with recent research (Abdel-Rahman et al, 2023). Notably, nicorandil pretreatment appeared to rectify this redox imbalance, suggesting a reversal of the detrimental effects of ATO on lung tissues.…”

Section: Discussionsupporting

confidence: 86%

Nicorandil mitigates arsenic trioxide‐induced lung injury via modulating vital signalling pathways SIRT1/PGC‐1α/TFAM, JAK1/STAT3, and miRNA‐132 expression

Abdel‐Wahab,

Zafaar,

Habeeb

et al. 2024

British J Pharmacology

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Background and PurposeNicorandil, a selective opener of potassium channels, used to treat angina, has drawn attention for its potential in mitigating lung injury, positioning it as a promising therapeutic approach to treat drug‐induced lung toxicity. This study aimed to explore the protective role of nicorandil in arsenic trioxide (ATO)‐induced lung injury and to elucidate the underlying mechanistic pathways.Experimental ApproachWe assessed the effects of nicorandil (15 mg·kg−1, p.o.) in a rat model of pulmonary injury induced by ATO (5 mg·kg−1, i.p.). The assessment included oxidative stress biomarkers, inflammatory cytokine levels, and other biomarkers, including sirtuin‐1, sirtuin‐3, STAT3, TFAM, and JAK in lung tissue. Histological examination using H&E staining and molecular investigations using western blotting and PCR techniques were conducted.Key ResultsIn our model of lung injury, treatment with nicorandil ameliorated pathological changes as seen with H&E staining, reduced tissue levels of toxicity markers, and exerted significant antioxidant and anti‐inflammatory actions. On a molecular level, treatment with nicorandil down‐regulated JAK, STAT3, PPARγ, Nrf2, VEGF, p53, and micro‐RNA 132 while up‐regulating Sirt1, 3, TFAM, AMPK, and ERR‐α in lung tissue.Conclusions and ImplicationsThe results presented here show nicorandil as a significant agent in attenuating lung injury induced by ATO in a rodent model. Nonetheless, further clinical studies are warranted to strengthen these findings.

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Section: Discussionsupporting

confidence: 86%

Nicorandil mitigates arsenic trioxide‐induced lung injury via modulating vital signalling pathways SIRT1/PGC‐1α/TFAM, JAK1/STAT3, and miRNA‐132 expression

Abdel‐Wahab,

Zafaar,

Habeeb

et al. 2024

British J Pharmacology

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Sorafenib and edaravone protect against renal fibrosis induced by unilateral ureteral obstruction via inhibition of oxidative stress, inflammation, and RIPK-3/MLKL pathway

Abou Taha,

Ali,

Saleh

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Renal fibrosis is the common endpoint of nearly all chronic and progressive nephropathies. Cell death and sterile inflammation are the main characteristics of renal fibrosis, which can lead to end-stage renal failure. The inflammatory reaction triggered by tissue damage is strongly related to necroptosis, a type of caspase-independent, regulated cell death. Using an animal model of unilateral ureteral obstruction (UUO), the anti-fibrotic effects of sorafenib (SOF), a multi-kinase inhibitor, and edaravone (EDV), a potent antioxidant and free radical scavenger, were examined in rats with obstructive nephropathy. Experimentally, animals were divided randomly into five groups: sham; UUO; UUO + SOF (5 mg/kg/day, P.O.); UUO + EDV (20 mg/kg/day, P.O.); and UUO + SOF + EDV groups. The kidney function biomarkers, oxidant/antioxidant status, renal mRNA expressions of TNF-α, collagen-1α, protein expressions of RIPK-1, RIPK-3, MLKL, caspase-8, HYP, MPO, and TNF-α were all significantly modulated by UUO. Administration of either SOF or EDV significantly attenuated cellular and molecular changes induced by UUO. Also, histopathological changes were improved. Moreover, SOF in combination with EDV, significantly improved UUO-induced renal fibrosis compared with each drug alone. Collectively, administration of either SOF or EDV or both of them significantly attenuated the rats with obstructive nephropathy, possibly by blocking the RIPK-3/MLKL necroptotic pathway and suppressing renal oxidative stress and inflammation.

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Vancomycin-induced acute kidney injury in rats: beneficial effects deriving from the co-administration of tadalafil or vitamin C

Mohammed,

Al-Saedi

2024

Rev. Clin. Pharmacol. Pharmacokinet., Int. Ed.

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Background: Vancomycin (VAN) is widely employed in clinical settings for the treatment of severe infections attributable to multi-resistant bacteria, with a notable emphasis on Gram-positive strains. However, its therapeutic usage is significantly hampered by the potential for acute kidney injury (AKI); specifically, the nephrotoxic effects it can exert. In controlled experimental studies, the intraperitoneal (i.p.) administration of VAN at a dose of 400 mg/kg/day over a consecutive seven-day period has been shown to induce considerable AKI in rats. In addressing this concern, vitamin C (VC), recognized traditionally for its antioxidant properties, has been utilized to mitigate various forms of organ damage and inflammatory responses, primarily by diminishing oxidative stress and attenuating inflammation. Concurrently, tadalafil (TAD), a phosphodiesterase type-5 inhibitor commonly associated with the treatment of erectile dysfunction, is also noted for its beneficial anti-inflammatory and antioxidant effects, alongside vasodilatory properties. Aim: This study was designed in order to investigate the protective capabilities of TAD or VC against the VAN-induced nephrotoxic effects in a rat model of AKI. Methodology: A total of 24 male albino Wistar rats were allocated into four distinct groups for the purpose of comparative analysis. Following treatment, both kidney and blood samples were obtained for further evaluation. The study randomized the rats into four categories: group 1 served as the control group, group 2 received VAN at a dosage of 400 mg/kg (via an i.p. injection on a daily basis), group 3 was administered VAN (400 mg/kg; i.p., daily) in conjunction with TAD at a dose of 5 mg/kg daily, and group 4 was given VAN (400 mg/kg; i.p., daily) alongside VC at a dosage of 200 mg/kg daily. Results: Evaluations included the measurement of renal function indicators such as the serum levels of urea, of creatinine, and the creatinine clearance. Additionally, the analysis involved the assessment of antioxidant markers in renal tissue homogenates, including malondialdehyde (MDA), glutathione, and superoxide dismutase. To further elucidate the inflammatory response, indices such as the levels of the tumor necrosis factor-alpha, the interleukins (IL)-1β and IL-6, and the nuclear factor-κB were evaluated within the renal tissue homogenate samples of the studied rats. The administration of VAN resulted in a marked elevation of renal biomarkers and inflammatory indices, alongside a significant reduction in antioxidant levels, with an exception for MDA (which exhibited increased levels); these changes reached statistical significance (p<0.05) when measured against the control group. In contrast, the supplementation with TAD or VC was effective in significantly lowering the serum levels of both renal and inflammatory indicators when compared to the group treated solely with VAN. Furthermore, antioxidant measurements improved, alongside a reduction in MDA levels, thereby demonstrating significant differences (p<0.05). Conclusion: The findings of this study reveal that both TAD and VC provide a degree of renal protection against the VAN-induced damage by enhancing kidney function markers and, concurrently, lessening oxidative stress and inflammatory responses associated with nephrotoxicity.

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Regulation of renal nitric oxide and eNOS/iNOS expression by tadalafil participates in the mitigation of amphotericin B–induced renal injury: Down-regulation of NF-κB/iNOS/caspase-3 signaling

Cited by 3 publications

References 66 publications

Nicorandil mitigates arsenic trioxide‐induced lung injury via modulating vital signalling pathways SIRT1/PGC‐1α/TFAM, JAK1/STAT3, and miRNA‐132 expression

Nicorandil mitigates arsenic trioxide‐induced lung injury via modulating vital signalling pathways SIRT1/PGC‐1α/TFAM, JAK1/STAT3, and miRNA‐132 expression

Sorafenib and edaravone protect against renal fibrosis induced by unilateral ureteral obstruction via inhibition of oxidative stress, inflammation, and RIPK-3/MLKL pathway

Vancomycin-induced acute kidney injury in rats: beneficial effects deriving from the co-administration of tadalafil or vitamin C

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