INVESTIGATION OF THE EFFECT OF OLANZAPINE AND L-CARNITINE ON RAT TESTIS TISSUE
Year 2023,
Volume: 30 Issue: 3, 284 - 293, 23.09.2023
Merve Akkuş
,
Faruk Kılıç
,
Halil Aşcı
,
Fatma Nihan Cankara
,
Mehtap Savran
,
Dilek Ulusoy Karatopuk
Abstract
Objective
Olanzapine has adverse effects on sexual dysfunction.
There are a limited number of studies showing that it
also causes structural changes in the reproductive
system. This study aimed to examine the effects of
L-Carnitine on testicular damage caused by Olanzapine
in terms of histopathological, sperm parameters, and
biochemical aspects.
Material and Method
A total of 48 adult Sprague-Dawley male rats were
used in our study. Rats were divided into 6 groups,
8 rats in each group: the Control group (C), 200 mg/
kg L-Carnitine administered group (LC), 2 mg/kg low
dose Olanzapine administered group (LOZN), 2 mg/kg
Olanzapine, and 200 mg/kg L-Carnitine administered
group (LOZN+LC), 4 mg/kg Olanzapine administered
group (HOZN), 4 mg/kg Olanzapine and 200 mg/
kg L-Carnitine administered group (HOZN+LC).
Testicular tissues were used for the determination of
MDA, IL-1B, IL-6, TAS, TOS levels, and histological
evaluation.
Results
In the groups receiving Olanzapine, a decrease in
sperm count, an increase in MDA, IL-1β, TOS values,
and dose-dependent histopathological changes in
testicular tissue were observed. Histopathological
changes were found at a lower rate in the Olanzapine
and L-Carnitine administered groups compared to the
Olanzapine-only groups.
Conclusion
It was concluded that the degenerative histological
findings in the testicular structure observed in the
high-dose Olanzapine administered groups might be
caused by the oxidative stress induced by Olanzapine
in the testicular tissue. L-Carnitine, on the other hand,
was thought to be effective in reducing testicular
degeneration by reducing oxidative damage.
Supporting Institution
This study was supported by the Süleyman Demirel University Scientific Research Project Office
Project Number
TTU-2018-6750.
Thanks
We thank Süleyman Demirel University Scientific Research Project Office for their support in this study.
References
- 1. Ardıç CM, Ilgın S, Baysal M, Karaduman AB, Kılıç V, Aydoğan-
Kılıç G, Uçarcan Ş, Atlı-Eklioğlu Ö. Olanzapine induced
reproductive toxicity in male rats. Sci Rep. 2021 Feb
26;11(1):4739. doi: 10.1038/s41598-021-84235-4. PMID:
33637793; PMCID: PMC7910427.
- 2. Katzung BG. Basic and Clinical Pharmacology 14th Edition:
McGraw Hill Professional; 2017.
- 3. Byerly MJ, Nakonezny PA, Bettcher BM, Carmody T, Fisher
R, Rush AJ. Sexual dysfunction associated with second-generation
antipsychotics in outpatients with schizophrenia or
schizoaffective disorder: an empirical evaluation of olanzapine,
risperidone, and quetiapine. Schizophrenia research.
2006;86(1-3):244-50
- 4. Bella AJ, Shamloul R. Psychotropics and sexual dysfunction.
Central European journal of urology. 2013;66(4):466
- 5. Cabello-Verrugio C, Simon F, Trollet C, Santibañez JF. Oxidative
Stress in Disease and Aging: Mechanisms and Therapies
2016. Oxid Med Cell Longev. 2017; 2017:4310469. doi:
10.1155/2017/4310469.
- 6. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative
stress, inflammation, and cancer: how are they linked? Free
Radic Biol Med. 2010 Dec 1;49(11):1603-16. doi: 10.1016/j.freeradbiomed.2010.09.006.
- 7. Sánchez A, Calpena AC, Clares B. Evaluating the Oxidative
Stress in Inflammation: Role of Melatonin. Int J Mol Sci. 2015
Jul 27;16(8):16981-7004. doi: 10.3390/ijms160816981.
- 8. Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N.
Oxidative Stress and Inflammation: What Polyphenols Can
Do for Us? Oxid Med Cell Longev. 2016; 2016:7432797. doi:
10.1155/2016/7432797.
- 9. Medzhitov R. Inflammation 2010: new adventures of an
old flame. Cell. 2010 Mar 19;140(6):771-6. doi: 10.1016/j.
cell.2010.03.006.
- 10. Seelaender M, Neto JC, Pimentel GD, Goldszmid RS, Lira
FS. Inflammation in the disease: mechanism and therapies
2014. Mediators Inflamm. 2015; 2015:169852. doi: 10.1155/2015/169852.
- 11. Lenzi A, Lombardo F, Sgrò P, Salacone P, Caponecchia L, Dondero
F, et al. Use of carnitine therapy in selected cases of male
factor infertility: a double-blind crossover trial. Fertility and sterility.
2003;79(2):292-300.
- 12. Gürbüz B, Yalti S, Fiçicioğlu C, Zehi˙ r K. Relationship between
semen quality and seminal plasma total carnitine in infertile
men. Journal of Obstetrics and Gynaecology. 2003;23(6):653-6.
- 13. Agarwal A, Sengupta P, Durairajanayagam D. Role of L-carnitine
in female infertility. Reprod Biol Endocrinol. 2018 Jan
26;16(1):5. doi: 10.1186/s12958-018-0323-4.
- 14. Mongioi L, Calogero A, Vicari E, Condorelli R, Russo G, Privitera
S, et al. The role of carnitine in male infertility. Andrology.
2016;4(5):800-7.
- 15. Vicari E, Calogero A. Effects of treatment with carnitines in
infertile patients with prostato-vesiculo-epididymitis. Human
Reproduction. 2001;16(11):2338-42.
- 16. Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine
in post-gonadal maturation of mammalian spermatozoa.
Human Reproduction Update. 1996;2(2):87-102.
- 17. Odaci E, Bilen H, Hacimuftuoglu A, Keles ON, Can İ, Bilici
M. Long-term treatments with low-and high dose olanzapine
change hepatocyte numbers in rats. A stereological
and histopathological study. Archives of medical research.
2009;40(3):139-45.
- 18. Mitchell M, Riesenberg R, Bari MA, Marquez E, Kurtz D, Falk
D, et al. A double-blind, randomized trial to evaluate the pharmacokinetics and tolerability of 30 or 40 mg/d oral olanzapine relative to 20 mg/d oral olanzapine in stable psychiatric subjects. Clinical therapeutics. 2006;28(6):881-92.
- 19. de Siqueira Bringel S, de Amorim Júnior AA, Amorim MJAAL,
Brito LT, Morais RN, de Torres SM, et al. Endocrine and testicular
changes induced by olanzapine in adult Wistar rats. Journal
of Applied Toxicology. 2013;33(1):24-31.
- 20. Terry AV Jr, Warner SE, Vandenhuerk L, Pillai A, Mahadik SP,
Zhang G, et al. Negative effects of chronic oral chlorpromazine
and olanzapine treatment on the performance of tasks designed
to assess spatial learning and working memory in rats.
Neuroscience. 2008;156(4):1005-16.
- 21. Yari A, Asadi MH, Bahadoran H, Dashtnavard H, Imani H, Naghii
MR. Cadmium toxicity in spermatogenesis and protective
effects of L-carnitine in adult male rats. Biological trace element
research. 2010;137(2):216-25.
- 22. Topcu-Tarladacalisir Y, Kanter M, Uzal MC. Role of L-carnitine
in the prevention of seminiferous tubules damage induced by
gamma radiation: a light and electron microscopic study. Archives
of toxicology. 2009;83(8):735-46.
- 23. Saudemont G, Prod'Homme C, Da Silva A, Villet S, Reich M,
Penel N, Gamblin V. The use of olanzapine as an antiemetic in
palliative medicine: a systematic review of the literature. BMC
Palliat Care. 2020 Apr 22;19(1):56. doi: 10.1186/s12904-020-
00559-4.
- 24. Soliman HM, Wagih HM, Attia GM, Algaidi SA. Light and electron
microscopic study on the effect of antischizophrenic drugs
on the structure of seminiferous tubules of adult male albino
rats. Folia histochemica et cytobiologica. 2014;52(4):335-49.
- 25. Deliktaş H, Gedik A, Nergiz Y, Bircan MK. The Effect of L-Carnitine
on Testicular Ischemia-Reperfusion Injury due to Testicular
Torsion in Rats. European Journal of General Medicine.
2012;9(3).
- 26. Kanter M, Topcu-Tarladacalisir Y, Parlar S. Antiapoptotic effect
of L-carnitine on testicular irradiation in rats. Journal of molecular
histology. 2010;41(2-3):121-8.
- 27. Coskun N, Hatipoglu MT, Ozogul C, Korkmaz C, Akyol SN, Micili
SC, et al. The protective effects of acetyl L-carnitine on testis
gonadotoxicity induced by Cisplatin in rats. Balkan medical
journal. 2013;30(2):235-41.
- 28. Khushboo M, Murthy MK, Devi MS, Sanjeev S, Ibrahim KS,
Kumar NS, et al. Testicular toxicity and sperm quality following
copper exposure in Wistar albino rats: ameliorative potentials
of L-carnitine. Environmental science and pollution research international.2018;25(2):1837-62.
- 29. Zare Z, Mohammadi M, Eimani H, Shafaroudi MM. Prevention
of di (2-ethylhexyl) Phthalate-induced Testicular Disturbance in
Mice by Co-administration of L-carnitine. International journal
of fertility & sterility. 2011;5(3):186.
- 30. Abo-Ghanema II, El-Nasharty M, El-Far A, Ghonium HA. Effect
of ginger and L-carnitine on the reproductive performance of
male rats. World Acad Sci Eng Technol. 2012; 64:980-6.
- 31. Yüksel N. Temel Psikofarmakoloji. Ankara, Türkiye Psikiyatri
Derneği. 2010.
- 32. Albaugh VL, Judson JG, She P, Lang CH, Maresca KP, Joyal
JL, et al. Olanzapine promotes fat accumulation in male
rats by decreasing physical activity, repartitioning energy and
increasing adipose tissue lipogenesis while impairing lipolysis.
Molecular psychiatry. 2011;16(5):569.
- 33. Pooyandjoo M, Nouhi M, Shab‐Bidar S, Djafarian K, Olyaeemanesh A. The effect of (L‐) carnitine on weight loss in adults: a systematic review and meta‐analysis of randomized controlled trials. Obesity reviews. 2016;17(10):970-6.
- 34. Davey KJ, O’Mahony SM, Schellekens H, O’Sullivan O, Bienenstock J, Cotter PD, et al. Gender-dependent consequences
of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology.2012;221(1):155-69.
- 35. Alahmar AT. Role of oxidative stress in male infertility: An
updated review. Journal of human reproductive sciences.
2019;12(1):4.
- 36. Mahmoud GS, El-Deek HE. Melatonin modulates inflammatory
mediators and improves olanzapine-induced hepatic steatosis
in rat model of schizophrenia. Int J Physiol Pathophysiol Pharmacol.
2019;11(3):64-75.
- 37. Eftekhari A, Azarmi Y, Parvizpur A, Eghbal MA. Involvement of
oxidative stress and mitochondrial/lysosomal cross-talk in olanzapine cytotoxicity in freshly isolated rat hepatocytes. Xenobiotica.2016;46(4):369-78.
- 38. Bilgic S, Korkmaz DT, Azirak S, Güvenc AN, Kocaman N, Ozer
MK. Olanzapine-induced renal damages and metabolic side effects: the protective effects of thymoquinone. Journal of Turgut
Ozal Medical Center. 2018;25(1).
- 39. Türkez H, Toğar B. The genotoxic and oxidative damage potential of olanzapine in vitro. Toxicology and industrial health.
2010;26(9):583-8.
- 40. Samanta L, Sahoo A, Chainy G. Age-related changes in rat testicular oxidative stress parameters by hexachlorocyclohexane.
Archives of toxicology. 1999;73(2):96-107.
- 41. Abarikwu SO, Adesiyan AC, Oyeloja TO, Oyeyemi MO, Farombi
EO. Changes in sperm characteristics and induction of oxidative
stress in the testis and epididymis of experimental rats
by a herbicide, atrazine. Archives of environmental contamination
and toxicology. 2010;58(3):874-82.
- 42. Shiraishi K, Takihara H, Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative
stress-mediated apoptosis. World journal of urology. 2010;28(3):359-64.
- 43. Aitken RJ, Baker MA. Oxidative stress and male reproductive
biology. Reproduction, Fertility and development. 2004;16(5):581-8.
- 44. Zini A, Libman J. Sperm DNA damage: clinical significance in
the era of assisted reproduction. Cmaj. 2006;175(5):495-500.
- 45. Kumar SB, Dada R, Gupta NP. Environmental Toxicants–Induced
Male Reproductive Toxicity: Role of Oxidative Stress. Bioenvironmental Issues Affecting Men's Reproductive and Sexual
Health: Elsevier; 2018. p. 305-22
- 46. Ding J, Shang X, Zhang Z, Jing H, Shao J, Fei Q, et al. FDA-approved medications that impair human spermatogenesis. Oncotarget.2017;8(6):10714.
- 47. Yanik TA, M. Sezlev, D. Kursungoz, C. Kurt, B. Akay, O. Akarsu,
S. Determination of Peripheral Gonadal Hormones after the
Treatment of Atypical Antipsychotics, Olanzapine and Risperidone
in Wistar Male Rats. The Endocrine Society's 94th Annual
Meeting and Expo. (2012);, June 23–26, Houston, TX.
OLANZAPİN VE L-KARNİTİNİN RAT TESTİS DOKUSU ÜZERİNDEKİ ETKİSİNİN ARAŞTIRILMASI
Year 2023,
Volume: 30 Issue: 3, 284 - 293, 23.09.2023
Merve Akkuş
,
Faruk Kılıç
,
Halil Aşcı
,
Fatma Nihan Cankara
,
Mehtap Savran
,
Dilek Ulusoy Karatopuk
Abstract
Amaç
Olanzapinin cinsel işlev bozukluğu üzerine olumsuz
etkileri vardır. Üreme sisteminde de yapısal değişikliklere
neden olduğunu gösteren sınırlı sayıda çalışma
bulunmaktadır. Bu çalışmada Olanzapinin neden olduğu
testis hasarı üzerine L-Karnitin'in etkilerinin histopatolojik,
sperm parametreleri, biyokimyasal açıdan
incelenmesi amaçlanmıştır.
Gereç ve Yöntem
Çalışmamızda toplam 48 adet erişkin Sprague-Dawley
erkek sıçan kullanıldı. Sıçanlar, her grupta 8 sıçan
olacak şekilde 6 gruba ayrıldı: Kontrol grubu (C), 200
mg/kg L-Karnitin uygulanan grup (LC), 2 mg/kg düşük
doz Olanzapin verilen grup (LOZN), 2 mg/kg Olanzapin
ve 200 mg/kg L-Karnitin verilen grup (LOZN+LC),
4 mg/kg Olanzapin verilen grup (HOZN), 4 mg/kg
Olanzapin ve 200 mg/kg L-Karnitin verilen grup (HOZN+
LC). MDA, IL-1B, IL-6, TAS, TOS düzeylerinin belirlenmesi,
histolojik değerlendirme için testis dokuları
kullanıldı.
Bulgular
Olanzapin alan gruplarda sperm sayısında azalma,
MDA, IL-1β, TOS değerlerinde artış, testis dokusunda
doza bağlı histopatolojik değişiklikler gözlendi.
Olanzapin ve L-Karnitin uygulanan gruplarda sadece
Olanzapin verilen gruplara göre histopatolojik değişiklikler
daha düşük oranda bulundu.
Sonuç
Yüksek doz Olanzapin uygulanan gruplarda gözlenen
testis yapısındaki dejeneratif histolojik bulguların,
Olanzapinin testis dokusunda oluşturduğu oksidatif
stresten kaynaklanabileceği sonucuna varıldı. L-Karnitin
ise oksidatif hasarı azaltarak testis dejenerasyonun
azaltılmasında etkili olabileceği düşünüldü.
Project Number
TTU-2018-6750.
References
- 1. Ardıç CM, Ilgın S, Baysal M, Karaduman AB, Kılıç V, Aydoğan-
Kılıç G, Uçarcan Ş, Atlı-Eklioğlu Ö. Olanzapine induced
reproductive toxicity in male rats. Sci Rep. 2021 Feb
26;11(1):4739. doi: 10.1038/s41598-021-84235-4. PMID:
33637793; PMCID: PMC7910427.
- 2. Katzung BG. Basic and Clinical Pharmacology 14th Edition:
McGraw Hill Professional; 2017.
- 3. Byerly MJ, Nakonezny PA, Bettcher BM, Carmody T, Fisher
R, Rush AJ. Sexual dysfunction associated with second-generation
antipsychotics in outpatients with schizophrenia or
schizoaffective disorder: an empirical evaluation of olanzapine,
risperidone, and quetiapine. Schizophrenia research.
2006;86(1-3):244-50
- 4. Bella AJ, Shamloul R. Psychotropics and sexual dysfunction.
Central European journal of urology. 2013;66(4):466
- 5. Cabello-Verrugio C, Simon F, Trollet C, Santibañez JF. Oxidative
Stress in Disease and Aging: Mechanisms and Therapies
2016. Oxid Med Cell Longev. 2017; 2017:4310469. doi:
10.1155/2017/4310469.
- 6. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative
stress, inflammation, and cancer: how are they linked? Free
Radic Biol Med. 2010 Dec 1;49(11):1603-16. doi: 10.1016/j.freeradbiomed.2010.09.006.
- 7. Sánchez A, Calpena AC, Clares B. Evaluating the Oxidative
Stress in Inflammation: Role of Melatonin. Int J Mol Sci. 2015
Jul 27;16(8):16981-7004. doi: 10.3390/ijms160816981.
- 8. Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N.
Oxidative Stress and Inflammation: What Polyphenols Can
Do for Us? Oxid Med Cell Longev. 2016; 2016:7432797. doi:
10.1155/2016/7432797.
- 9. Medzhitov R. Inflammation 2010: new adventures of an
old flame. Cell. 2010 Mar 19;140(6):771-6. doi: 10.1016/j.
cell.2010.03.006.
- 10. Seelaender M, Neto JC, Pimentel GD, Goldszmid RS, Lira
FS. Inflammation in the disease: mechanism and therapies
2014. Mediators Inflamm. 2015; 2015:169852. doi: 10.1155/2015/169852.
- 11. Lenzi A, Lombardo F, Sgrò P, Salacone P, Caponecchia L, Dondero
F, et al. Use of carnitine therapy in selected cases of male
factor infertility: a double-blind crossover trial. Fertility and sterility.
2003;79(2):292-300.
- 12. Gürbüz B, Yalti S, Fiçicioğlu C, Zehi˙ r K. Relationship between
semen quality and seminal plasma total carnitine in infertile
men. Journal of Obstetrics and Gynaecology. 2003;23(6):653-6.
- 13. Agarwal A, Sengupta P, Durairajanayagam D. Role of L-carnitine
in female infertility. Reprod Biol Endocrinol. 2018 Jan
26;16(1):5. doi: 10.1186/s12958-018-0323-4.
- 14. Mongioi L, Calogero A, Vicari E, Condorelli R, Russo G, Privitera
S, et al. The role of carnitine in male infertility. Andrology.
2016;4(5):800-7.
- 15. Vicari E, Calogero A. Effects of treatment with carnitines in
infertile patients with prostato-vesiculo-epididymitis. Human
Reproduction. 2001;16(11):2338-42.
- 16. Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine
in post-gonadal maturation of mammalian spermatozoa.
Human Reproduction Update. 1996;2(2):87-102.
- 17. Odaci E, Bilen H, Hacimuftuoglu A, Keles ON, Can İ, Bilici
M. Long-term treatments with low-and high dose olanzapine
change hepatocyte numbers in rats. A stereological
and histopathological study. Archives of medical research.
2009;40(3):139-45.
- 18. Mitchell M, Riesenberg R, Bari MA, Marquez E, Kurtz D, Falk
D, et al. A double-blind, randomized trial to evaluate the pharmacokinetics and tolerability of 30 or 40 mg/d oral olanzapine relative to 20 mg/d oral olanzapine in stable psychiatric subjects. Clinical therapeutics. 2006;28(6):881-92.
- 19. de Siqueira Bringel S, de Amorim Júnior AA, Amorim MJAAL,
Brito LT, Morais RN, de Torres SM, et al. Endocrine and testicular
changes induced by olanzapine in adult Wistar rats. Journal
of Applied Toxicology. 2013;33(1):24-31.
- 20. Terry AV Jr, Warner SE, Vandenhuerk L, Pillai A, Mahadik SP,
Zhang G, et al. Negative effects of chronic oral chlorpromazine
and olanzapine treatment on the performance of tasks designed
to assess spatial learning and working memory in rats.
Neuroscience. 2008;156(4):1005-16.
- 21. Yari A, Asadi MH, Bahadoran H, Dashtnavard H, Imani H, Naghii
MR. Cadmium toxicity in spermatogenesis and protective
effects of L-carnitine in adult male rats. Biological trace element
research. 2010;137(2):216-25.
- 22. Topcu-Tarladacalisir Y, Kanter M, Uzal MC. Role of L-carnitine
in the prevention of seminiferous tubules damage induced by
gamma radiation: a light and electron microscopic study. Archives
of toxicology. 2009;83(8):735-46.
- 23. Saudemont G, Prod'Homme C, Da Silva A, Villet S, Reich M,
Penel N, Gamblin V. The use of olanzapine as an antiemetic in
palliative medicine: a systematic review of the literature. BMC
Palliat Care. 2020 Apr 22;19(1):56. doi: 10.1186/s12904-020-
00559-4.
- 24. Soliman HM, Wagih HM, Attia GM, Algaidi SA. Light and electron
microscopic study on the effect of antischizophrenic drugs
on the structure of seminiferous tubules of adult male albino
rats. Folia histochemica et cytobiologica. 2014;52(4):335-49.
- 25. Deliktaş H, Gedik A, Nergiz Y, Bircan MK. The Effect of L-Carnitine
on Testicular Ischemia-Reperfusion Injury due to Testicular
Torsion in Rats. European Journal of General Medicine.
2012;9(3).
- 26. Kanter M, Topcu-Tarladacalisir Y, Parlar S. Antiapoptotic effect
of L-carnitine on testicular irradiation in rats. Journal of molecular
histology. 2010;41(2-3):121-8.
- 27. Coskun N, Hatipoglu MT, Ozogul C, Korkmaz C, Akyol SN, Micili
SC, et al. The protective effects of acetyl L-carnitine on testis
gonadotoxicity induced by Cisplatin in rats. Balkan medical
journal. 2013;30(2):235-41.
- 28. Khushboo M, Murthy MK, Devi MS, Sanjeev S, Ibrahim KS,
Kumar NS, et al. Testicular toxicity and sperm quality following
copper exposure in Wistar albino rats: ameliorative potentials
of L-carnitine. Environmental science and pollution research international.2018;25(2):1837-62.
- 29. Zare Z, Mohammadi M, Eimani H, Shafaroudi MM. Prevention
of di (2-ethylhexyl) Phthalate-induced Testicular Disturbance in
Mice by Co-administration of L-carnitine. International journal
of fertility & sterility. 2011;5(3):186.
- 30. Abo-Ghanema II, El-Nasharty M, El-Far A, Ghonium HA. Effect
of ginger and L-carnitine on the reproductive performance of
male rats. World Acad Sci Eng Technol. 2012; 64:980-6.
- 31. Yüksel N. Temel Psikofarmakoloji. Ankara, Türkiye Psikiyatri
Derneği. 2010.
- 32. Albaugh VL, Judson JG, She P, Lang CH, Maresca KP, Joyal
JL, et al. Olanzapine promotes fat accumulation in male
rats by decreasing physical activity, repartitioning energy and
increasing adipose tissue lipogenesis while impairing lipolysis.
Molecular psychiatry. 2011;16(5):569.
- 33. Pooyandjoo M, Nouhi M, Shab‐Bidar S, Djafarian K, Olyaeemanesh A. The effect of (L‐) carnitine on weight loss in adults: a systematic review and meta‐analysis of randomized controlled trials. Obesity reviews. 2016;17(10):970-6.
- 34. Davey KJ, O’Mahony SM, Schellekens H, O’Sullivan O, Bienenstock J, Cotter PD, et al. Gender-dependent consequences
of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology.2012;221(1):155-69.
- 35. Alahmar AT. Role of oxidative stress in male infertility: An
updated review. Journal of human reproductive sciences.
2019;12(1):4.
- 36. Mahmoud GS, El-Deek HE. Melatonin modulates inflammatory
mediators and improves olanzapine-induced hepatic steatosis
in rat model of schizophrenia. Int J Physiol Pathophysiol Pharmacol.
2019;11(3):64-75.
- 37. Eftekhari A, Azarmi Y, Parvizpur A, Eghbal MA. Involvement of
oxidative stress and mitochondrial/lysosomal cross-talk in olanzapine cytotoxicity in freshly isolated rat hepatocytes. Xenobiotica.2016;46(4):369-78.
- 38. Bilgic S, Korkmaz DT, Azirak S, Güvenc AN, Kocaman N, Ozer
MK. Olanzapine-induced renal damages and metabolic side effects: the protective effects of thymoquinone. Journal of Turgut
Ozal Medical Center. 2018;25(1).
- 39. Türkez H, Toğar B. The genotoxic and oxidative damage potential of olanzapine in vitro. Toxicology and industrial health.
2010;26(9):583-8.
- 40. Samanta L, Sahoo A, Chainy G. Age-related changes in rat testicular oxidative stress parameters by hexachlorocyclohexane.
Archives of toxicology. 1999;73(2):96-107.
- 41. Abarikwu SO, Adesiyan AC, Oyeloja TO, Oyeyemi MO, Farombi
EO. Changes in sperm characteristics and induction of oxidative
stress in the testis and epididymis of experimental rats
by a herbicide, atrazine. Archives of environmental contamination
and toxicology. 2010;58(3):874-82.
- 42. Shiraishi K, Takihara H, Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative
stress-mediated apoptosis. World journal of urology. 2010;28(3):359-64.
- 43. Aitken RJ, Baker MA. Oxidative stress and male reproductive
biology. Reproduction, Fertility and development. 2004;16(5):581-8.
- 44. Zini A, Libman J. Sperm DNA damage: clinical significance in
the era of assisted reproduction. Cmaj. 2006;175(5):495-500.
- 45. Kumar SB, Dada R, Gupta NP. Environmental Toxicants–Induced
Male Reproductive Toxicity: Role of Oxidative Stress. Bioenvironmental Issues Affecting Men's Reproductive and Sexual
Health: Elsevier; 2018. p. 305-22
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