Mahmoud Ghada S, El-Deek Heba Em
Department of Medical Physiology, Faculty of Medicine, Assiut University Assiut, Egypt.
Department of Pathology, Faculty of Medicine, Assiut University Assiut, Egypt.
Int J Physiol Pathophysiol Pharmacol. 2019 Jun 15;11(3):64-75. eCollection 2019.
Melatonin (Mel) has lower levels and can be used as monotherapy in schizophrenia. Mel alleviated liver steatosis induced by atypical antipsychotics.
To investigate Mel effect as monotherapy and addon treatment on ketamine-induced behavioral changes in rat schizophrenia model and olanzapine (Ola)-induced metabolic derangement.
24 male rats divided into four groups; C: control; O: Ola; OM: Ola plus Mel and M: Mel. All groups treated orally daily for 25 days. We measured activities of daily life (ADL) and rat performance in radial arm water maze (RAWM) before and after ketamine (Ket) injection, serum level of liver enzymes, lipoproteins, sugar, inflammatory markers and liver histopathology.
Ket significantly reduced burrowing and hoarding behavior, increased working memory errors (WME) and time to reach target (TRT). Ola antagonized the deleterious effects of Ket on ADL, WME and TRT. Mel monotherapy significantly reduced burrowing and doesn't affect hoarding, WME or TRT in RAWM. Significant rise in ALT, AST, IL-1 beta, IL-6, IL-10, TNF-alpha, LDL, TGs and hepatic steatosis score (HSS) in O compared to C group. Co administration of Mel significantly decreased ALT, AST, IL-1 beta, IL-6 and TNF alpha. Insignificant difference in IL-10, TGs or LDL and significant improvement in HSS in OM compared to O group. Insignificant change in HDL or blood sugar in both O and OM groups compared to C group detected.
Although ineffective as monotherapy, Mel co administration provides promising natural way to improve Ola-induced hepatic derangement in psychotic disorders.
褪黑素（Mel）水平较低，可用于精神分裂症的单一疗法。Mel可减轻非典型抗精神病药物引起的肝脂肪变性。
研究Mel作为单一疗法和辅助治疗对氯胺酮诱导的大鼠精神分裂症模型行为变化及奥氮平（Ola）诱导的代谢紊乱的影响。
将24只雄性大鼠分为四组；C组：对照组；O组：Ola组；OM组：Ola加Mel组；M组：Mel组。所有组每天口服给药25天。我们在注射氯胺酮（Ket）前后测量了日常生活活动（ADL）和大鼠在放射状臂水迷宫（RAWM）中的表现、肝酶、脂蛋白、血糖、炎症标志物的血清水平以及肝脏组织病理学。
Ket显著降低了挖掘和囤积行为，增加了工作记忆错误（WME）和到达目标的时间（TRT）。Ola拮抗了Ket对ADL、WME和TRT的有害影响。Mel单一疗法显著降低了挖掘行为，且不影响RAWM中的囤积行为、WME或TRT。与C组相比，O组的ALT（谷丙转氨酶）、AST（谷草转氨酶）、IL-1β、IL-6、IL-10、TNF-α（肿瘤坏死因子-α）、LDL（低密度脂蛋白）、TGs（甘油三酯）和肝脏脂肪变性评分（HSS）显著升高。Mel联合给药显著降低了ALT、AST、IL-1β、IL-6和TNF-α。与O组相比，OM组的IL-10、TGs或LDL无显著差异，HSS有显著改善。与C组相比，O组和OM组的HDL（高密度脂蛋白）或血糖无显著变化。
尽管作为单一疗法无效，但Mel联合给药为改善精神疾病中Ola诱导的肝脏紊乱提供了一种有前景的天然方法。
