Doxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) is a naturally occurring diterpene in unfiltered coffee with unique antioxidant, antimutagenic, and anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate the potential chemoprotective effect of cafestol on DOX-induced cardiotoxicity in rats. Wistar albino rats of both sexes were administered cafestol (5 mg/kg/day) for 14 consecutive days by oral gavage alone or with doxorubicin which was injected as a single dose (15 mg/kg intraperitoneally at day 14) to induce toxicity. The result showed that Caf significantly improved cardiac injury induced by doxorubicin, decreased serum levels of CK-MB, LDH, ALP, and ALT, and improved histopathological changes. In addition, cafestol significantly inhibited DOX-induced cardiac oxidative stress as seen in the reduced level of MDA and increased GSH, SOD, CAT, and Gpx-1 cardiac tissue levels; cafestol significantly enhanced Nrf2 gene and protein expression and promoted the expression of downstream antioxidant genes HO-1 and NQO-1 and downregulated Keap1 and NF-κB genes’ expression; in addition, Caf significantly reduced inflammatory mediators, TNF-α, and IL-1β levels and inhibited cardiac apoptosis by modulating Bax and Casp 3 tissue levels and reduced TUNEL-positive cardiomyocytes. In conclusion, the present study confirmed that cafestol improved the cardiotoxic effects induced by doxorubicin through the regulation of apoptosis and oxidative stress response through the Nrf2 pathway; this study suggests that cafestol may serve as a potential adjuvant in chemotherapy to alleviate DOX-induced toxicities.
Cardiac toxicity can occur during the therapy with several cytotoxic drugs, including 5- Fluorouracil (5- FU). It is an antimetabolite that acts during the S phase of the cell cycle and is activated by thymidine phosphorylase into fluorodeoxyuridylate (5 fluoro 2'deoxyuridine 5'monophosphate, 5-FdUMP) that inhibits thymidylate synthase, thus preventing DNA synthesis that leads to imbalanced cell growth and ultimately cell death. It is still a widely used anticancer drug, since 1957. The present study aimed to evaluate the possible cardio-protective effects of ethanolic artichoke extract (Cynara scolymus L.) against 5-fluorouracil (5-FU) induced cardio-toxicity in rats by evaluating serum levels of Alanine aminotransferase, aspartate amin
... Show MoreBackground: Cyclophosphamide (Cpd), a common immunosuppressive and chemotherapeutic drug, can cause hepatotoxicity by inducing inflammation and oxidative stress. Dapagliflozin (Dapa) and other sodium-glucose cotransporter-2 inhibitors (SGLT2i) have anti-inflammatory and antioxidant properties, and Silymarin is a natural compound extracted from the seeds of the milk thistle plant (Silybum marianum). It is best known for its antioxidant, anti-inflammatory, and hepatoprotective effects.Objective: By measuring oxidative stress, inflammation, and liver regeneration parameters, with an emphasis on the Nrf2/HO-1 pathway and hepatocyte nuclear factors (HNF4α and HNF6), Dapa's hepatoprotective effects in comparison to Sil on Cpd-induced liv
... Show MoreDrug-induced acute kidney injury is a serious disorder. Oxidative stress has a key role in its initiation and progression. In this study, the possible ameliorative effect of fimasartan against methotrexate-induced nephrotoxicity was investigated in comparison with α-tocopherol in rats. Wistar rats were allocated into six groups and treated as follows: group Ӏ received water on a daily basis for 8 successive days; group ӀӀ received methotrexate (20 mg/kg) on day 1, followed by water for 7 successive days; group ӀӀӀ received fimasartan (3 mg/kg/day) for 7 successive days; group IV received α-tocopherol (1 g/kg/day) for 7 successive days; group V re
... Show MoreAbstract: Fluoroquinolones drugs are an important class of wide
... Show MoreBackground: Cyclophosphamide is an alkylating agent that is effective against a broad spectrum of tumors, with nephrotoxicity as a side effect. Irigenin is a natural isoflavonoid isolated from the rhizome of Belamcanda chinensis that has been reported to exert antioxidant activities. Objective: Evaluating the possible protective effects of irigenin on cyclophosphamide-induced nephrotoxicity in male rats. Methods: Fifty apparently healthy male albino rats were divided into five groups: (control, induction, irigenin, irigenin with cyclophosphamide, and vitamin E with cyclophosphamide. At the end of the experiment (day 29), all rats were sacrificed. Different parameters were evaluated, including urea and creatinine serum concentration,
... Show MoreThe objective of this study was to evaluate the impact two doses of Menaquinones-7 on hepatotoxicity induced by doxorubicin in rats. Sixty adult rats of both sexes were used in this study; the animals were randomly enrolled into six groups of 10 animals each. Group I: negative control (rats administered distilled water); Group II: Menaquinones-7 at a dose of 16 µg/kg; Group III: Menaquinones-7 at a dose of 48 µg/kg; Group IV: positive control (Doxorubicin 15 mg/kg); Group V: Menaquinones-7 at a dose of 16 µg/kg administered prior to a single dose of Doxorubicin 15 mg/kg; Group VI: Menaquinones-7 at a dose of 48 µg/kg administered prior to a single dose of Doxorubicin 15 mg/kg. On day twelve of the study, blood was
... Show MoreBackground: Cisplatin (CDDP) is an effective chemotherapeutic agent whose gonadotoxicity can lead to premature ovarian insufficiency through oxidative stress, inflammation, and apoptosis. Sodium–glucose cotransporter-2 (SGLT2) inhibitors exhibit cytoprotective effects, but their ovarian effects during chemotherapy remain poorly defined. Methods: Twenty-four female Wistar rats were randomized (n = 6/group) to Control (vehicle), Cisplatin (7 mg/kg, i.p., day 14), Cisplatin + dapagliflozin (DAPA; 0.9 mg/kg/day, p.o., days 1–14), or Cisplatin + empagliflozin (EMPA; 10 mg/kg/day, p.o., days 1–14). At 24 h post-cisplatin, serum estradiol (E2), progesterone, follicle-stimulating hormone (FSH), and Anti-Müllerian Hormone (AMH) were measured
... Show MoreIrinotecan induced-mucositis is an inflammatory event of intestine caused by an increase in concentration of active metabolite 7ethyl10-hydroxycamptothecin (SN38) in the intestine. Irinotecan must first be converted by a carboxylesterase (CES) to the active metabolite (SN38), which is subsequently glucuronidated by the hepatic enzyme to SN38G. The SN-38G is deconjugated in the intestine to SN-38 via ?-glucuronidase produced by the intestinal bacterial flora, which accounts for SN-38 delayed intestinal mucositis of irinotecan. To study the protective effect of mentha in irinotecan-induced mucositis, intestinal mucositis induced by I.P injection of irinotecan (75mg/Kg/day) for 4 days. Mentha ethanolic extract orally administered to
... Show MoreThis study aimed to see how allicin (45mg/kg BW) affected diabetic Mellitus in male rats (DM). Forty male rats were utilized, and they were split into four groups at random for 42 days. T2 was treated with 45 mg/kg B.W of allicin dissolved in 1 ml of D.W daily and injected with a single dose of sodium citrate buffer (0.5ml Intra-Peritoneal IP), DM was induced in T1 and T2 by injection of a single dose of streptozotocin 50 mg/kg B.W IP, T1 was assigned as a positive control, T3 received 45 mg/kg B.W. of allicin dissolved in 1 ml D.W. every day, and a single dose of sodium citrate buffer was injected (0.5ml IP). When diabetic rats treated with allicin in T2 were compared to diabetic rats in T1, the findings indicated a significant increase (P
... Show MoreThe aim of this study is to investigate the protective effect of Radish (Raphanus sativus) seed alcoholic extract 70% against oxidative stress induced by sodium nitrite NaNO2 Twenty five adult male rabbits were devided into five groups of (five rabbits in each group) and treated daily for 30 days. Group T1: intubated orally 20 mg/kg NaNO2, Group T2: intubated orally 20 mg/kg NaNO2 + 50 mg/kg of alcoholic extract from Raphanus sativus seeds, Group T3: intubated orally 20 mg/kg NaNO2 + 100 mg/kg of alcoholic extract from Raphanus sativus seeds, Group T4: intubated orally 20 mg/kg NaNO2 + 200 mg/kg of alcoholic extract from Raphanus sativus seed as well as Group C: control intubated orally distilled water. In comparison with normal ra
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