title: Lopinavir/Ritonavir, an Antiretroviral Drug, Lowers Sperm Quality and Induces Testicular Oxidative Damage in Rats.
abstract: BACKGROUND
  Lopinavir/Ritonavir (Kaletra®) is a protease inhibitor used in the management of HIV infection. The increased incidence of toxicity of antiretroviral therapy (ART) has necessitated proper evaluation of their effects on reproductive health.
  
  
  OBJECTIVE
  Therefore, this study was designed to investigate the effects of Kaletra® on male reproductive system in Wistar rat.
  
  
  METHODS
  Eighteen rats were assigned into three groups. The first group served as control while the second and third groups received Kaletra® at therapeutic dose (8.3 mg/kg) (Kaletra-T) and twice therapeutic dose (16.6 mg/kg) (Kaletra-2T). Kaletra® was given orally for 21 days.
  
  
  RESULTS
  Administration of Kaletra® caused a significant (p = 0.023) decrease in body weight-gain of rats. Precisely, Kaletra-T and Kaletra-2T decreased body weight-gain by 43% and 48%, respectively. Kaletra-T and kaletra-2T significantly (p = 0.016-0.036) decreased sperm motility and sperm count while kaletra-2T increased total sperm abnormalities in the rats. Also, Kaletra® (at the two doses) caused a significant (p = 0.02-0.04) increase in the levels of testicular lipid peroxidation with a concomitant decrease in antioxidant indices. Specifically, Kaletra-T and Kaletra-2T decreased the activities of glutathione peroxidase by 38% and 57%, catalase by 40% and 48%, glutathione-s-transferase by 32% and 35% and superoxide dismutase by 47% and 52%, respectively while Kaletra-2T decreased reduced glutathione by 49%. Photomicrographs of testis from control and Kaletra-T groups showed normal seminiferous tubules with abundant spermatogenic cells while Kaletra-2T group had few and abnormal shape spermatogenic cells.
  
  
  CONCLUSIONS
  Kaletra® induces oxidative damage in testis of rats leading to changes in sperm characteristics and antioxidant status of the animals.
authors.affiliation: Department of Biochemistry, University of Ibadan, Ibadan, Nigeria. aoadaramoye@yahoo.com.
authors.forename: Oluwatosin A
authors.initials: OA
authors.lastname: Adaramoye
authors.forename: Olubukola O
authors.initials: OO
authors.lastname: Akanni
authors.forename: Olubusuyi M
authors.initials: OM
authors.lastname: Adewumi
authors.forename: Solomon E
authors.initials: SE
authors.lastname: Owumi
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D017208:Rats, Wistar; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000002:abnormalities*; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000378:metabolism*
chemical_list: D044966:Anti-Retroviral Agents; D000975:Antioxidants; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D019438:Ritonavir