Nicotinamide attenuates cyclophosphamide‐induced hepatotoxicity in SD rats by reducing oxidative stress and apoptosis

Patwa, Jayant; Khan, Sabbir; Jena, Gopabandhu

doi:10.1002/jbt.22558

Cited by 18 publications

(12 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cellular status of overwhelmed oxidative agents accompanied by decreased antioxidant contents is described as oxidative stress. As documented by many recent reports [ 5–7 , 10 , 18 ], oxidative stress in liver of CP-injected mice was evidenced in the present study by the increased level of MDA, protein carbonyl, and NO and by decreased GSH levels and antioxidant enzymes (SOD and CAT) activities. Increased lipid peroxidation causes alterations in membrane fluidity and membrane integrity, thus disrupting membrane permeability [ 57 ].…”

Section: Discussionsupporting

confidence: 84%

Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling

et al. 2023

View full text Add to dashboard Cite

Taxifolin (TA) is a natural flavonoid found in many foods and medicinal plants with well-documented antioxidant and anti-inflammatory properties. Cyclophosphamide (CP) is an effective antineoplastic and immunosuppressive agent; however, it is associated with numerous adverse events, including hepatotoxicity. Herein, we aimed to investigate the potential protective effects of TA using a mouse model of CP-induced hepatotoxicity. Mice were co-treated with TA (25 and 50 mg/kg, orally) and CP (30 mg/kg, i.p.) for 10 consecutive days and sacrificed 24 hours later. CP induced increased transaminases (ALT and AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) paralleled with pronounced histopathological alterations in the liver. Moreover, hepatic tissues of CP-injected mice showed increased malondialdehyde (MDA), protein carbonyl, and nitric oxide (NO) levels, accompanied by decreased antioxidant defenses (glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT]). Livers of CP-injected mice also showed increased inflammatory response (NF-κB p65 activation, increased levels of proinflammatory cytokines tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β] and IL-6) and apoptosis (decreased Bcl-2 and increased Bax and caspase-3 expression levels). Remarkably, TA ameliorated markers of liver injury and histological damage in CP-injected mice. TA treatment also attenuated numerous markers of oxidative stress, inflammation, and apoptosis in the liver of CP-injected mice. This was accompanied by increased nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase 1 (HO-1) expression in the liver tissues of CP-injected mice. Taken together, this study indicates that TA may represent a promising new avenue to prevent/treat CP-induced hepatotoxicity and perhaps other liver diseases associated with oxidative stress and inflammation.

show abstract

Section: Discussionsupporting

confidence: 84%

Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling

et al. 2023

View full text Add to dashboard Cite

show abstract

“…These data suggested the CK1A signaling partly explained the mechanism of NAM on the lens regeneration. In addition, NAM is best known in enhancing cell survival, improving reprogramming, facilitating differentiation, regulating DNA repair, suppressing apoptosis and promoting the development and self-renewal, which is a multifunctional factor [20,[41][42][43]. Therefore, we would repeat the in vitro lenses regeneration for RNAseq analysis and specific transgenic mouse models for better understanding of the…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide improves in vitro lens regeneration in a mouse capsular bag model

et al. 2022

View full text Add to dashboard Cite

Background Mammalian lens regeneration holds great potential as a cataract therapy. However, the mechanism of mammalian lens regeneration is unclear, and the methods for optimization remain in question. Methods We developed an in vitro lens regeneration model using mouse capsular bag culture and improved the transparency of the regenerated lens using nicotinamide (NAM). We used D4476 and SSTC3 as a casein kinase 1A inhibitor and agonist, respectively. The expression of lens-specific markers was examined by real-time PCR, immunostaining, and western blotting. The structure of the in vitro regenerated lens was investigated using 3,3′-dihexyloxacarbocyanine iodide (DiOC6) and methylene blue staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and transmission electron microscopy. Results The in vitro lens regeneration model was developed to mimic the process of in vivo mammalian lens regeneration in a mouse capsular bag culture. In the early stage, the remanent lens epithelial cells proliferated across the posterior capsule and differentiated into lens fiber cells (LFCs). The regenerated lenses appeared opaque after 28 days; however, NAM treatment effectively maintained the transparency of the regenerated lens. We demonstrated that NAM maintained lens epithelial cell survival, promoted the differentiation and regular cellular arrangement of LFCs, and reduced lens-related cell apoptosis. Mechanistically, NAM enhanced the differentiation and transparency of regenerative lenses partly by inhibiting casein kinase 1A activity. Conclusion This study provides a new in vitro model for regeneration study and demonstrates the potential of NAM in in vitro mammalian lens regeneration.

show abstract

“…Despite of clinical applications of CP, it has adverse in uence on the liver that decomposes CP to active metabolites, on the kidney that excretes it. The previous studies have shown that impaired humoral secretion, infertility, DNA damage, lipid peroxidation and morphological defects in the tissues are associated to the treatment with the CP (Patwa & Khan, 2020).…”

Section: Introductionmentioning

confidence: 99%

Saponin protects against cyclophosphamide-induced kidney and liver damage via antioxidant and anti-inflammatory actions

Golmohammadi

Banaei

Timar

et al. 2023

PhysInt

View full text Add to dashboard Cite

BackgroundThe liver and kidney are organs affected by chemotherapy drugs such as cyclophosphamide (CP). This study examined the protective effects of treatment with saponin (SP) against CP-induced nephrotoxicity and hepatotoxicity.Methods24 adult male mice were divided into four groups (N = 6): Control group, CP (15 mg kg−1), SP (2.5 mg kg−1) and CP + SP. After treatment, blood samples were collected for the determination of biochemical parameters. Liver and kidney samples were taken for histological analysis and assessment of oxidative stress and inflammatory markers.ResultsCyclophosphamide decreased renal and liver functions and antioxidant enzymes, which significantly increased blood urea nitrogen and creatinine (BUN, Cr), liver enzyme levels, malondialdehyde, nuclear factor kappa β (NF-kB) and Interleukin 1 beta (IL-1B) concentrations. Moreover, histopathological findings of the CP group showed that there were acute tubular necrosis and glomerular atrophy in the renal tissues and lymphocyte infiltration in the liver samples. Treatment with saponin improved hepatic and renal functions, pathological changes and antioxidant capacity, and also decreased lipid peroxidation and inflammation.ConclusionIt seems that saponin could exert a hepato-nephroprotective effect against cyclophosphamide toxicity.

show abstract

Nicotinamide attenuates cyclophosphamide‐induced hepatotoxicity in SD rats by reducing oxidative stress and apoptosis

Cited by 18 publications

References 63 publications

Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling

Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling

Nicotinamide improves in vitro lens regeneration in a mouse capsular bag model

Saponin protects against cyclophosphamide-induced kidney and liver damage via antioxidant and anti-inflammatory actions

Contact Info

Product

Resources

About