Dataset Information

Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model.

ABSTRACT:

Background

The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy.

Methods

Male Sprague-Dawley rats were randomly divided into 3 groups: a control group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor (TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV) tissues from each group.

Results

Losartan administration reduced LV hypertrophy, collagen content, and the expression of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment induced a reduction in the apoptotic area compared to group A.

Conclusion

In an ADR-induced cardiomyopathy rat model, co-administration of ADR with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory factors, and apoptosis in LV tissue.

SUBMITTER: Kim HA

PROVIDER: S-EPMC10480395 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model.

Kim Hyeon A HA Kim Kwan Chang KC Lee Hyeryon H Hong Young Mi YM

Journal of chest surgery 20230814 5

<h4>Background</h4>The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy.<h4>Methods</h4>Male Sprague-Dawley rats were randomly divided into 3 groups: ...[more]

PMID: 37574884

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Project description:BackgroundDA-9401 was prepared as a mixture of Chinese medicinal herb extracts from roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae). The present study was designed to investigate the possible protective role of DA-9401 in adriamycin (ADR)-induced testicular toxicity associated with oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis.MethodsFifty healthy 8-week-old male Sprague-Dawley rats were equally divided into five groups. The first CTR group was treated with normal saline 2 ml/day by gavage. The second was treated with DA-100 (DA-9401 100 mg/kg/day). The third (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and DA-9401 was given to the fourth ADR + DA-100 (100 mg/kg/day p.o) group and fifth ADR + DA-200 (200 mg/kg/day p.o) group. At the end of the 8-week treatment period, body weight, reproductive organ weights, fertility rate, pups per female were recorded, and serum were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathological changes, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), oxidative stress markers and expression levels of endoplasmic reticulum (ER) stress markers, apoptosis markers, tight junction protein markers, steroidogenic acute regulatory protein (StAR), cation channel of sperm (CatSper) and glycogen synthase kinase-3 (GSK-3) by western blot.ResultsDA-9401 administration to ADR-treated rats significantly decreased serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, interleukin-6, TNF-α, MDA level, ROS/RNS level, ER stress response protein levels, tunnel positive cells, cleaved caspase-3, and Bax/Bcl2 ratio. Moreover, pretreatment with DA-9401 significantly increased body weight, reproductive organ weights, fertility rate, pups per female, Johnsen's score, spermatogenic cell density, sperm count and sperm motility, serum testosterone concentration, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), tight junction protein markers, star protein level, CatSper, and GSK-3 level.ConclusionsADR treatment can markedly impair testicular function and induce testicular cell death presumably by causing significant changes in oxidative stress, ER stress, and mitochondrial pathway. DA-9401 exerts beneficial effects against oxidative stress, ER stress, and mitochondria-mediated cell death pathway in testis tissue by up-regulating expression levels of tight junction protein markers, steroidogenic acute regulatory protein, GSK-3 alpha, and cation channels of sperm.

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Dataset Information

Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model.

Background

Methods

Results

Conclusion

Publications

Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model.

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