Abstract Mitoxantrone is an antitumor agent used in the treatment of breast and prostate cancer, acute leukemia, lymphoma, and also in the treatment of multiple sclerosis due to its immunosuppressive properties. The mitoxantrone's cardiotoxicity is irreversible, dose-dependent, and it may occur years after treatment. Zinc is considered as an essential mineral for cell division and the synthesis of DNA and protein; furthermore, such mineral has an important role in states of cardiovascular diseases; and may have protective effects in coronary artery disease and cardiomyopathy. Objective: The current study is designed to investigate effects of two different doses of zinc sulfate on mitoxantrone-induced cardiotoxicity in rats. Methods: Forty-eight (48) adult rats of both sexes were utilized in this study; the animals were randomly divided into six groups of 8 animals each. Group I: distilled water (negative control). Group II: orally-administered zinc sulfate (15mg/kg/day) Group III: orally-administered zinc sulfate (30mg/kg/day) Group IV: Intraperitoneally injected with a mitoxantrone at a dose (2.5 mg/kg) to reach total cumulative dose of 7.5 mg/kg on day 20. Group V: Orally-administered zinc sulfate at a dose (15mg/kg/day) and an intraperitoneal injection of mitoxantrone at a dose (2.5 mg/kg) was administered to reach total cumulative dose of 7.5 mg/kg on day 20. Group VI: Orally-administered zinc sulfate at a dose (30 mg/kg/day), and an intraperitoneal injection of mitoxantrone at a dose (2.5 mg/kg) to reach total cumulative dose of 7.5 mg/kg on day 20. Forty-eight (48) hr after the end of treatment duration (i.e. at day 22 nd), each animal was euthanized by diethyl ether and ketamine. Then, after cervical dislocation, blood was obtained by intracardiac puncture and then serum was prepared to estimate cardiac troponin I 3 enzyme activity levels; and the heart of each animal was excised for homogenate preparation to estimate of malondialdehyde contents. Results: Oral administration of zinc sulfate [(15mg/kg/day with total cumulative dose (7.5 mg/kg) of mitoxantrone] (Group V) resulted in a non-significant (P>0.05) difference in serum activity level of troponin I 3 enzyme and malondialdehyde contents in cardiac tissue homogenate compared to the corresponding serum enzyme activity level and contents in group of rats intraperitoneally injected with total cumulative dose of 7.5 mg/kg of mitoxantrone (Group IV). In contrast, there were significant reduction (P<0.05) in serum activity level of troponin I 3 enzyme and malondialdehyde contents in cardiac tissue homogenate of rats orally-administered zinc sulfate [(30 mg/kg/day) with total cumulative dose (7.5mg/kg) of mitoxantrone] (Group VI) compared to the corresponding enzyme activity levels and contents in group of rats intraperitoneally-injected with total cumulative dose of 7.5mg/kg of mitoxantrone (Group IV). Conclusion: zinc sulfate at a dose (30 mg/kg/day) diminishes the cardiotoxicity induced by mitoxantrone via a free radical scavenger property but it is non signifant compared to (15 mg/kg/day) .
Abstract
Mitoxantrone is an antitumor agent used in the treatment of breast and prostate cancer, acute leukemia, lymphoma, and also in the treatment of multiple sclerosis due to its immunosuppressive properties. The mitoxantrone's cardiotoxicity is irreversible, dose-dependent, and it may occur years after treatment. Zinc is considered as an essential mineral for cell division and the synthesis of DNA and protein; furthermore, such mineral has an important role in states of cardiovascular diseases; and may have protective effects in coronary artery disease and cardiomyopathy.
Objective: The current study is designed to investigate effects of two different doses of zinc sulfat
... Show MoreCiprofloxacin is widely used in treating adults infected with Gram-negative bacteria. It is contraindicated in children, growing adolescents and during pregnancy due to joint toxicity. Its toxicity concerning other organs needs to be clarified. Thus, this study was designed to study the possible cardiac damage induced by two selected doses of ciprofloxacin in juvenile rats.Eighteenth healthy juvenile rats (4 weeks old and their weight 30 ± 2 gm) were utilized in this study and divided into three groups. Group-I control; group II and group III, respectively injected IP with 25 mg/kg and 50 mg/kg ciprofloxacin every 12 hours for one week. Serum enzymes activities alanine aminotransferase (ALT), aspartate aminotransferase (AST), cr
... Show MoreThe nephrotoxicity induced by methotrexate is a severe condition that greatly affects its therapeutic potential and has a significant inflammatory component. Fimasartan is an angiotensin receptor blocker that offers organ-protective effects and may be useful in mitigating renal injury. The present study explored the anti-inflammatory potential of two doses of fimasartan against methotrexate-mediated nephrotoxicity. Albino rats were intraperitoneally administered a single methotrexate (20 mg/kg). Intraperitoneal treatment with fimasartan (5 or 10 mg/kg/day) was initiated on day two after methotrexate injection and continued for seven consecutive days. Methotrexate significantly increased serum urea, creatinine, and NGAL concentrations. It al
... Show MoreAbstract Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rats through the involvement of Nrf2
... Show MoreThe liver protective effects of pentoxifylline were studied through pre-treatment of rats with various intraperitoneal (IP) doses (25, 50 and 100mg/kg/day) 14 days before induction of liver toxicity by carbon tetrachloride (CCl4). The parameters of oxidative stress, malondialdehyde (MDA) and reduced glutathione (GSH) were measured in liver homogenate in addition to histopathological examinations. Analysis of data revealed significant amelioration of oxidative stress in groups of animals pre-treated with different doses of pentoxifylline (PTX) compared to group of animals intoxicated by CCl4 as evidenced by lowering MDA contents and elevation of GSH levels in liver tissue homogenate but the levels still signifi
... Show MoreAbstract
Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rat
... Show MoreAbstract: The aim of the current study was to investigate the possible protective effect of graded doses (5, 10, and 15mg/kg) of pyridoxine hydrochloride intraperitoneally injected against (15mg/kg) doxorubicin-induced cardiotoxicity in female rats. Fifty-six (56) Wistar albino female rats were utilized weighing 180-200 gm allocated into eight groups, seven rats each; Group I: negative control distilled water; Group II: Pyridoxine (5mg/kg); Group III: Pyridoxine (10mg/kg); Group IV: Pyridoxine (15mg/kg); Group V: doxorubicin (15 mg/kg); Group VI: Pyridoxine (5 mg/kg) prior to doxorubicin (15 mg/kg); Group VII: Pyridoxine (10 mg/kg) prior to doxorubicin (15 mg/kg); Group VIII: Pyridoxine (15 mg/kg) prior to doxorub
... 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 is a widely used antineoplastic drug in different types of cancers (ovarian, testicular, and hematological) with several types of adverse effects, including testicular toxicity. Fimasartan is a newer angiotensin-receptor blocker (ARB) that has antioxidant and anti-inflammatory properties. Omega-3 is an unsaturated fatty acid that has antioxidant and anti-inflammatory effects. Objective: to evaluate the protective effects of fimasartan alone or in combination with omega-3 against cisplatin-induced testicular toxicity. Methods: Thirty Wistar rats were divided into five groups: control group, cisplatin-treated group, fimasartan+cisplatin group, fimasartan+omega-3+cisplatin group, and omega-3+cisplatin group. Trea
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