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Alpha-lipoic acid may ameliorate testicular damage by targeting dox-induced altered antioxidant parameters,
Elif Erdem Guzel1, Nalan Kaya Tektemur2, Ahmet Tektemur3
1Department of Midwifery, Faculty of Health Sciences, Mardin Artuklu University, Mardin, Turkey.
Abstract:
In the study, the ameliorating effects of alfa lipoic acid (ALA) against doxorubicin-induced testicular apoptosis, oxidative stress and disrupted mitochondrial fusion were investigated in male rats. Rats were divided into four groups as control, doxorubicin (DOX), DOX + ALA and ALA. A single dose of 15 mg/kg DOX was administered i.p to the DOX and DOX + ALA groups. 50 mg/kg ALA was given to the DOX + ALA and ALA groups by oral gavage every other day. After 28 days, rat testes and serum samples were collected and analysed. Administration of DOX alone caused a decrease in body and relative testicular weights, seminiferous tubule diameter and germinal epithelium thickness, Johnsen's score and serum testosterone levels. DOX treatment led to severe testicular damage such as tubular degeneration, and atrophic tubules. Also, the activities of superoxide dismutase and glutathione peroxidase were reduced, while the level of malondialdehyde was increased in the testis. The mRNA levels of apoptotic-related genes (CASP3, TP53, BAX, BCL2) and apoptotic index were increased, while mitofusin-2 decreased. DOX caused an increase in CASP3 and a decrease in mitofusin-2 immunoreactivities. Treatment with ALA markedly improved all of DOX-induced biochemical, histochemical and molecular alterations in rat testis. Consequently, ALA has a therapeutic role in ameliorating DOX-induced testicular damage in rats.
Insights
Alpha lipoic acid (ALA) protects against doxorubicin (DOX)-induced testicular damage in rats. ALA treatment reversed DOX-induced apoptosis, oxidative stress, and mitochondrial dysfunction, preserving testicular health.
Area of Science:
- Reproductive toxicology
- Mitochondrial biology
- Oxidative stress research
Background:
- Doxorubicin (DOX) is a potent chemotherapy agent with known testicular toxicity.
- DOX-induced damage involves apoptosis, oxidative stress, and impaired mitochondrial dynamics.
- Alpha-lipoic acid (ALA) is an antioxidant with potential protective properties.
Purpose of the Study:
- To investigate the protective effects of ALA against DOX-induced testicular damage in male rats.
- To evaluate ALA's impact on apoptosis, oxidative stress, and mitochondrial fusion markers in DOX-treated testes.
Main Methods:
- Male rats were divided into four groups: control, DOX, DOX + ALA, and ALA.
- DOX (15 mg/kg) was administered intraperitoneally; ALA (50 mg/kg) was given orally every other day for 28 days.
- Testicular and serum samples were analyzed for biochemical, histochemical, and molecular changes, including gene expression and protein immunoreactivity.
Main Results:
- DOX treatment significantly reduced body weight, testicular weight, seminiferous tubule diameter, germinal epithelium thickness, Johnsen's score, and testosterone levels.
- DOX induced testicular degeneration, increased oxidative stress markers (malondialdehyde), decreased antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase), and elevated apoptotic markers (CASP3, TP53, BAX, BCL2).
- DOX treatment decreased mitofusin-2 expression, indicating disrupted mitochondrial fusion. ALA administration markedly improved all these DOX-induced alterations.
Conclusions:
- Doxorubicin causes significant testicular damage through apoptosis, oxidative stress, and mitochondrial dysfunction.
- Alpha-lipoic acid demonstrates a significant therapeutic role in ameliorating doxorubicin-induced testicular toxicity in rats.
- ALA may be a promising agent for protecting male reproductive health during chemotherapy.
