Jul 2026· Journal of biochemical and molecular toxicology· Vol 40· 0 citations· 67 references
Medicine
TL;DR
RUPA counteracts hepatotoxicity evoked by CISP in rats via its anti‐oxidative as well as anti‐inflammatory properties via repression of hepatic HMGB1/TLR4/NF‐κB and thus restricts the activation of NLRP3/caspase‐1 signaling cascade.
Abstract
Despite cisplatin (CISP) is broadly employed in cancer therapy, its adverse effects, involving hepatotoxicity, restrict its clinical usage. Thus, this study was designed to explore the prospect of repurposing rupatadine (RUPA), a dual antagonist of histamine and platelet‐activating factor (PAF), against CISP‐evoked hepatotoxicity in rats. Rats were i.p. injected with CISP (6 mg/kg) for the induction of hepatotoxicity on the 8th day of the study in the presence and absence of RUPA in two dosages (3, 6 mg/kg) orally for 14 days. Different biochemical parameters and histopathological assessments, along with the mechanistic characterizations of the possible protective impact of the RUPA were conducted. Administration of CISP evoked hepatic histopathological modifications and raised serum liver enzyme levels and hepatic MDA content, PAF, and histamine levels, along with diminishing the serum albumin level, hepatic SOD activity, and GSH level. Moreover, CISP remarkably augmented the levels of HMGB1, TLR4, p‐NF‐κB p65, IL‐6, TNF‐α, IL‐18, IL‐1β, NLRP3, and cleaved caspase‐1 proteins with an evident decline in the level of IL‐10. On the contrary, pretreatment with either RUPA.3 or RUPA.6 dramatically ameliorated these alterations triggered by CISP injection. RUPA counteracts hepatotoxicity evoked by CISP in rats via its anti‐oxidative as well as anti‐inflammatory properties via repression of hepatic HMGB1/TLR4/NF‐κB and thus restricts the activation of NLRP3/caspase‐1 signaling cascade.
N-Cur mitigates oxidative damage and inflammation, thereby preserving hepatic function during CDDP-based chemotherapy, and demonstrates significant potential as a hepatoprotective agent when administered concomitantly with CDDP chemotherapy.
Q. Alqahtani, M. Atteya, T. Almatrafi et al.· Biomedicines· 0 citations
ABSTRACT Hepatotoxicity is one of the most crucial side effects of chemotherapy administration. Obeticholic acid (OCA) is a semisynthetic bile acid and farnesoid X receptor (FXR) agonist derived from chenodeoxycholic acid, with reported antioxidant and anti‐inflammatory effects in liver disorders. This study investigated the hepatoprotective effect of OCA against commonly used chemotherapy cisplatin (CP)‐induced hepatotoxicity in rats, as well as the modulatory effects of edaravone (EDA), a potent free radical scavenger, on its effects. Rats were divided into five groups: control (received vehicle), CP (7.5 mg/kg), EDA (30 mg/kg) + CP, OCA (30 mg/kg) + CP, and EDA + OCA + CP. The results of the present study demonstrated that both OCA and EDA significantly mitigated liver damage caused by CP, as evidenced by restoring liver enzymes and histological structure, reestablishment of oxidant/antioxidant status, suppression of inflammation, and attenuation of pro‐death signaling. The study highlights the role of key molecular pathways, including Keap1/Nrf2/HO‐1,HO‐1, TNF‐α/NF‐κB, and AKT/GSK‐3β, in the hepatoprotective mechanisms of OCA. Collectively, these findings suggest that OCA and EDA, particularly in combination, attenuate CP‐induced hepatotoxicity and are associated with coordinated modulation of oxidative stress, inflammatory signaling, and AKT/GSK‐3β‐associated pro‐survival/pro‐death pathways.
Fares E. M. Ali, Adel G. Bakr, Abdel-Gawad S. Shalkami et al.· Journal of biochemical and m...· 0 citations
Doxorubicin (DOX) is an anticancer antibiotic that is widely utilized. Nevertheless, this therapeutic potential is hampered by its cardiotoxicity. Alogliptin (ALO), an antidiabetic, recently is being repurposed for the management of various organs ailments owing to its discovered biological activities as an antioxidant, anti-inflammatory, anti-apoptotic and antifibrotic through multiple pathways. This study is directed to evaluate the possible protective effect of ALO against DOX-induced cardiac molecular and histopathological alterations. Twenty-four adult Wistar rats were grouped into control in addition to ALO (20 mg/kg, p.o, 21 days), DOX (18 mg/kg, i.p; six equal divided doses on alternative days starting at day 8), and Dox + ALO treated groups. On the 21st day, blood samples are collected to assess cardiac biomarkers. Additionally, the hearts of all rats were separated and processed for histological evaluation, ultrastructural examination, and collagen content determination by Masson Triciumus staining, and biochemical studies. The DOX group had pronounced deleterious histological and ultrastructural disorganization accompanied with abundant collagen disposition. Biochemically, DOX group demonstrated significant elevation of cardiomyocytes content of MDA, NF-κB, TNF-α, IL-6, BAX, and TGF-β1 which mirrored as significantly elevated serum LDH, CKMB, and cTnI levels. However, SOD and CAT activities as well as GSH, BCL-2, SIRT3 and NRF2 content along with miRNA-133a gene expression are significantly decreased. Present results proved the prophylactic ALO antioxidant, anti-inflammatory, anti-apoptotic, and anti-fibrotic influence on the DOX-induced cardiotoxicity with proposed mechanisms entailing the activation of SIRT3 pathway that may be governed by miRNA-133a. However, these results are limited by the inspection lack of echocardiography or hemodynamic alterations, gain and loss of function, caspase activation, and mitochondrial health tests. Thus, ALO has the potential to be an appropriate therapy for DOX-induced cardiotoxicity.
N. F. Elmongy, Mohamed Ali Abbas, S. Elshora et al.· Tissue & Cell· 0 citations
Rosmarinus officinalis extract may exert protective effects against MTX-induced hepatorenal injury through antioxidant and anti-inflammatory mechanisms, however, further studies are required to confirm these effects and validate their therapeutic potential.
Lana Muhammed, Nadia Salih· Open Veterinary Journal· 0 citations
BACKGROUND
Ivabradine (IVA), a broad-spectrum inhibitor of HCN cation channels, is recognized for enhancing cardiac function in the treatment of cardiovascular diseases and may serve as a potential therapeutic agent for mitigating drug-induced cardiotoxicity. This study aimed to investigate the protective effect of IVA against cardiac damage induced by cisplatin (Cis) and to elucidate the underlying mechanisms.
METHODS
We investigated the impact of IVA (5 mg/kg, orally for 28 consecutive days) on Cisplatin-induced cardiac injury (7.5 mg/kg intraperitoneally on day 5) in rats. Biomarkers of oxidative stress and levels of inflammatory cytokines in cardiac tissue were assessed. H&E staining was employed to identify histopathological alterations in cardiac tissue. The molecular mechanisms of IVA in ameliorating cardiac injury were examined.
RESULTS
The results indicated that IVA enhanced cardiac tissue structure by suppressing the pathological alterations observed in H&E staining. IVA demonstrated antioxidant and anti-inflammatory properties through reducing malonaldehyde (MDA), NADPH oxidase, tumor necrosis factor-α (TNF-α), and interleukins (IL-1β and IL-6) levels, while elevating superoxide dismutase (SOD), IL-10, and eNOS levels. IVA diminished the expression of cAMP response element-binding protein (CREB), Extracellular signal-regulated kinase (ERK), Mitogen-activated protein kinase kinase (MEK), Protein Kinase C-epsilon (PKC epsilon), and microRNA-34a (miRNA-34a), while enhancing the expression of Protein Kinase G (PKG), Myosin Light Chain Phosphatase (MLCP), and Rapidly Accelerated Fibrosarcoma (Raf-1), as confirmed by western blotting and PCR results. Furthermore, its impact on cardiac tissue viability was supported by increased B-cell lymphoma 2 (Bcl2) levels and decreased caspase-3 staining in immunohistopathology.
CONCLUSION
IVA may significantly mitigate cardiac injury in Cis-induced cardiotoxicity through regulating multiple pathways and miRNA-34a levels.
N. Aldabaan, BaselA Abdel-Wahab, Ehab A. M. El-Shoura et al.· Immunopharmacology and immun...· 0 citations
Arsenic trioxide (ATO) is a potent therapeutic agent against acute promyelocytic leukemia; nevertheless, its clinical utility is severely restricted by dose-limiting nephrotoxicity. This study investigated the protective potential of a radiation-synthesized gallotannin hydrogel (GTH) against ATO-induced kidney injury in rats. Forty male Wistar rats were randomized into four experimental groups: Control, ATO (4 mg/kg, i.p., for 4 weeks), GTH (2 mg/kg, i.p.), and ATO + GTH. GTH treatment was initiated during the third week of ATO administration, with GTH being administrated one hour prior to ATO injection. Following the experimental period, animals were sacrificed, tissue histology was examined, and renal function was assessed by serum urea and creatinine levels. Oxidative stress was evaluated via MDA, SOD, GSH, and GPx markers. Additionally, miR-223 and TXNIP expression levels were quantified using qRT-PCR. Inflammatory mediators (NF-κB, NLRP3, Caspase-1, IL-1β, and IL-18), endoplasmic reticulum (ER) stress markers (PERK, eIF2α, and CHOP), and the apoptotic marker caspase-3 were analyzed by ELISA. Our results revealed that GTH noticeably ameliorated kidney dysfunction, as evidenced by reduced serum urea and creatinine levels. Furthermore, GTH attenuated oxidative stress by decreasing MDA levels and restoring antioxidant enzyme activities (SOD, GSH, and GPx). Histological analysis confirmed that GTH mitigated structural renal damage. Molecularly, GTH administration suppressed the ATO-induced upregulation of miR-223 and TXNIP. This downregulation correlated with a reduction in inflammatory mediators, attenuation of ER stress markers, and decreased apoptosis. These findings demonstrate that radiation-synthesized gallotannin hydrogel (GTH) exerts nephroprotective effects against ATO-induced nephrotoxicity. These benefits are driven by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms mediated via modulation of the miR-223/TXNIP axis.
Omayma A. R. Abo-Zaid, Mostafa A. Farrag, Aya S. R. Shaaban et al.· Biological Trace Element Res...· 0 citations
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