The combined effect of honey and olive oil against methotrexate mediated hepatotoxicity in rats: A biochemical, histological and immunohistological study

Background. Honey and olive oil are natural products that have high nutritional values, and therapeutic properties. Cytotoxic drugs, like methotrexate (MTX) are used to treat malignancies in tumour cells; however, these drugs also have serious side effects that could threaten the patient's life. Aim. To evaluate the potential protective effects of honey and olive oil, administered alone or together, against MTX-induced hepatotoxicity in rats. Methods. Adult male albino rats were divided: Group I: negative control (n=8); II: honey (daily by oral 1.2 g/kg bwt (n=8), III: olive oil (1 ml/day) (n=8), IV: single intraperitoneal injection of MTX (20 mg/kg bwt) (n=8), V: diluted honey for 3 days before injection of MTX (n=8), Group VI: olive oil for 3 days before injection of MTX (n=8), Group VII: both honey and olive oil for 3 days before injection of MTX (n=8). After treatment, rats were sacrified and blood samples were collected to determine liver function parameters, liver tissue used to measure the oxidative (malondialdehyde), antioxidative parameters (superoxide dismutase, catalase and glutathione peroxidase), histological and immunohistochemical techniques. Results. The administration of honey and olive oil exerted a protective effect against MTX-induced hepatotoxicity, as demonstrated by the normalization of the liver enzymes, proteins and total bilirubin and by the histopathological and immunohistological changes observed in the livers. Both agents also reversed the oxidative damage in the liver by decreasing level of MDA levels and increasing the antioxidant related by enzymes in the liver homogenates compared to the control rats. These effects were more evident when the two agents were administered together. Conclusion. The combined intake of honey and olive oil could be hepatoprotective. Co-administration of these agents might form an effective adjuvant therapy and minimize side effects of chemoherapy in cancerous patients

The Impact of Chronic Unpredictable Mild Stress-Induced Depression on Spatial, Recognition and Reference Memory Tasks in Mice: Behavioral and Histological Study

Depression-induced cognitive impairment has recently been given more attention in research. However, the relationship between depression and different types of memory is still not clear. Chronic unpredictable mild stress (CUMS) is a commonly used animal model of depression in which animals are exposed to chronic unpredictable environmental and psychological stressors, which mimics daily human life stressors. This study investigated the impact of different durations of CUMS on various types of memory (short- and long-term spatial memory and recognition memory) and investigated CUMS’ impact on the ultrastructural level by histological assessment of the hippocampus and prefrontal cortex. Twenty male C57BL/J6 mice (6 weeks old, 21.8 ± 2 g) were randomly divided into two groups (n = 10): control and CUMS (8 weeks). A series of behavioral tasks were conducted twice at weeks 5–6 (early CUMS) and weeks 7–8 (late CUMS). A tail-suspension test (TST), forced swimming test (FST), elevated zero maze (EZM), elevated plus maze (EPM), open field test (OFT), and sucrose-preference test (SPT) were used to assess anxiety and depressive symptoms. The cognitive function was assessed by the novel object recognition test (NORT; for recognition memory), Y-maze (for short-term spatial memory), and Morris water maze (MWM: for long-term spatial memory) with a probe test (for reference memory). Our data showed that 8 weeks of CUMS increased the anxiety level, reported by a significant increase in anxiety index in both EPM and EZM and a significant decrease in central preference in OFT, and depression was reported by a significant increase in immobility in the TST and FST and sucrose preference in the SPT. Investigating the impact of CUMS on various types of memory, we found that reference memory is the first memory to be affected in early CUMS. In late CUMS, all types of memory were impaired, and this was consistent with the abnormal histological features of the memory-related areas in the brain (hippocampus and prefrontal cortex)