Histopathological and Histomorphometric studies on the effects of Olanzapine on Testis: An experimental study in Albino Rats
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The Preventive Effect of Zinc Sulfate against Olanzapine-Induced Testicular Toxicity in Male Rats
Male infertility is a complex and multifactorial clinical condition affecting a large population attributed to several factors, including perturbation in oxidative stress and the level of essential trace elements. Oxidative stress exerts multiple issues related to reproductive health, including male infertility, decreased sperm motility, sperm DNA damage, and an increased susceptibility to genetic disorders. Besides chemical toxins and food allergens in junk food items, many drugs can also lead to male infertility. Olanzapine (OLZ), a general antipsychotic drug, has also been reported to induce male fertility. A great deal of literature entails that supplementation of zinc can alleviate oxidative stress–related clinical complications, including male infertility. This study investigates the potential protective effects of zinc sulfate (ZnSO4) on OLZ-induced male infertility. In the present study, there were four treatment groups (n = 6): group 1 as control (without any treatment); group 2 treated with OLZ (10 mg/kg) orally daily for 6 weeks; groups 3 and 4 treated with 50 mg/kg and 100 mg/kg of ZnSO4 respectively in pre-exposed OLZ (10 mg/kg) orally daily for 6 weeks. After completion of the treatment, the biochemical analysis of serum and tissue samples demonstrated that group 2 had compromised levels of antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)) as well as elevated levels of stress parameters (oxidized glutathione (GSSG), malondialdehyde (MDA), and nitric oxide (NO)) as compared to the control by a significant extent (p ≤ 0.05). However, supplementation of ZnSO4 significantly corrected all these parameters in a dose-dependent way in groups 3 and 4 (p ≤ 0.05). Other health indicators, like taurine, enzyme Q10, phosphatidylcholine, ascorbic acid, and vitamin E, were also observed to improve prominently with the supplementation of ZnSO4. Intriguingly, all the fertility parameters (sperm motility, count and level of testosterone) were also found to be significantly enhanced with decreased sperm abnormalities in both the combination groups. The histological evaluation of the testis section also agreed with the biochemical analysis in this investigation. Therefore, the study strongly advocates that supplementation of Zn can ameliorate OLZ-induced male infertility to a significant extent. Graphical Abstract Putative mechanism was involved in a preventive effect of ZnSO4 against OLZ-induced biochemical and histological perturbation in vivo. OLZ generates free radicals to induce oxidative stress-mediated toxicity in all target organs including testes evidenced by alteration in biochemical markers and histology. Zn ions from ZnSO4 act as an antioxidant agent blunting most of the OLZ-perturbed redox markers and histology consequently improving fertility parameters.
The Preventive Effect of Zinc Sulfate against Olanzapine-Induced Testicular Toxicity in Male Rats
Male infertility is a complex and multifactorial clinical condition affecting a large population attributed to several factors, including perturbation in oxidative stress and the level of essential trace elements. Oxidative stress exerts multiple issues related to reproductive health, including male infertility, decreased sperm motility, sperm DNA damage, and an increased susceptibility to genetic disorders. Besides chemical toxins and food allergens in junk food items, many drugs can also lead to male infertility. Olanzapine (OLZ), a general antipsychotic drug, has also been reported to induce male fertility. A great deal of literature entails that supplementation of zinc can alleviate oxidative stress–related clinical complications, including male infertility. This study investigates the potential protective effects of zinc sulfate (ZnSO4) on OLZ-induced male infertility. In the present study, there were four treatment groups (n = 6): group 1 as control (without any treatment); group 2 treated with OLZ (10 mg/kg) orally daily for 6 weeks; groups 3 and 4 treated with 50 mg/kg and 100 mg/kg of ZnSO4 respectively in pre-exposed OLZ (10 mg/kg) orally daily for 6 weeks. After completion of the treatment, the biochemical analysis of serum and tissue samples demonstrated that group 2 had compromised levels of antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)) as well as elevated levels of stress parameters (oxidized glutathione (GSSG), malondialdehyde (MDA), and nitric oxide (NO)) as compared to the control by a significant extent (p ≤ 0.05). However, supplementation of ZnSO4 significantly corrected all these parameters in a dose-dependent way in groups 3 and 4 (p ≤ 0.05). Other health indicators, like taurine, enzyme Q10, phosphatidylcholine, ascorbic acid, and vitamin E, were also observed to improve prominently with the supplementation of ZnSO4. Intriguingly, all the fertility parameters (sperm motility, count and level of testosterone) were also found to be significantly enhanced with decreased sperm abnormalities in both the combination groups. The histological evaluation of the testis section also agreed with the biochemical analysis in this investigation. Therefore, the study strongly advocates that supplementation of Zn can ameliorate OLZ-induced male infertility to a significant extent. Graphical Abstract Putative mechanism was involved in a preventive effect of ZnSO4 against OLZ-induced biochemical and histological perturbation in vivo. OLZ generates free radicals to induce oxidative stress-mediated toxicity in all target organs including testes evidenced by alteration in biochemical markers and histology. Zn ions from ZnSO4 act as an antioxidant agent blunting most of the OLZ-perturbed redox markers and histology consequently improving fertility parameters.
Zinc sulphate alleviates olanzapine-induced testicular oxidative stress and alters trace elements in male rats
Male infertility is a complex and multifactorial clinical condition affecting a large population attributed to various factors, including perturbation in oxidative stress and the level of essential trace elements. Oxidative insults exert multiple issues related to reproductive health, including male infertility, decreased sperm motility, sperm DNA damage, and an increased susceptibility to genetic disorders. Besides chemical toxins and food allergens in junk food items, many drugs can also lead to male fertility. Olanzapine, a general antipsychotic drug, has also been reported to induce male fertility. A great deal of literature entails that zinc can alleviate oxidative stress-related clinical complications including male fertility. This study investigates the potential protective effects of zinc sulphate on olanzapine-induced male infertility. In the present study, there were four treatment groups (n = 6) Group 1 as control (without any treatment); Group 2 treated with olanzapine (10 mg/kg) orally daily for six weeks; Group 3 and 4 treated with 50mg/kg and 100 mg/kg of zinc sulphate respectively in pre-exposed olanzapine (10mg/kg) orally daily for six weeks. After completion of the treatment, the biochemical analysis of serum and tissue samples demonstrated that group 2 had compromised levels of antioxidant parameters (SOD, CAT and GSH) as well as elevated levels of stress parameters (GSSG, MDA and NO). However, ZnSO4 corrected all these parameters in a dose-dependent way in groups 3 and 4. Other health indicators, like taurine, enzyme Q10, phosphatidylcholine, ascorbic acid, and vitamin E, were also observed to improve with the supplementation of ZnSO4. Intriguingly, all the fertility parameters (sperm motility, count and level of testosterone) were also found to significantly enhanced with decreased sperm abnormalities in both the combination groups. The histological evaluation of the testis section also agreed with the biochemical analysis. Therefore, the study strongly advocates that supplementation of Zn can ameliorate olanzapine-induced male infertility to a significant extent.
The reprotoxic adverse side effects of neurogenic and neuroprotective drugs: current use of human organoid modeling as a potential alternative to preclinical models
The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health.
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