Zinc Ameliorate Oxidative Stress and Hormonal Disturbance Induced by Methomyl, Abamectin, and Their Mixture in Male Rats

Exposure to mixtures of toxicants (e.g., pesticides) is common in real life and a subject of current concern. The present investigation was undertaken to assess some toxicological effects in male rats following exposure to methomyl (MET), abamectin (ABM), and their combination (MET+ABM), and to evaluate the ameliorative effect of zinc co-administration. Three groups of rats were designated for MET, ABM, and the mixture treatments. Three other groups were designated for zinc in conjunction with the pesticides. Additionally, one group received water only (control), and the other represented a positive zinc treatment. The obtained results revealed that MET was acutely more toxic than ABM. The tested pesticides induced significant elevation in lipid peroxidation and catalase levels, while declined the levels of the other tested parameters e.g., Superoxide dismutase (SOD), Glutathione-S-transferase (GST), Glutathione peroxidase (GPx), Glutathione reductase (GR), Cytochrome P450 (CYP450), testosterone, and thyroxine). Biochemical alterations induced by the mixture were greater than those recorded for each of the individual insecticides. The joint action analysis, based on the obtained biochemical data, revealed the dominance of antagonistic action among MET and ABM. Zinc supplementation achieved noticeable ameliorative effects. It was concluded that zinc may act as a powerful antioxidant, especially in individuals who are occupationally exposed daily to low doses of such pesticides

Which exposure stage (gestation or lactation) is more vulnerable to atrazine toxicity? Studies on mouse dams and their pups

Either during gestation or lactation, the experimental mouse dams received one of the following treatments: (a) diet free of pesticide; (b) diet enriched with atrazine (ATZ); 31.0 μg kg−1; (c) diet free of pesticide + oral vitamin E (α-tocopherol; 200 mg kg−1 per mouse); and (d) diet enriched with ATZ (31.0 μg kg−1) + oral vitamin E (200 mg kg−1 per mouse). At the weaning, pups and dams were killed and selected organs and blood samples were collected for analyses. Compared with the control results, ATZ induced alteration in a number of biochemical and histopathological parameters either in the dams or their offspring. The ameliorative effect of vitamin E, based on estimating the “Ameliorative Index; AI” to malondialdehyde (MDA) and superoxide dismutase (SOD) ranged between 0.95 and 1.06 (≈1.0) for the dams and the pups either in gestational or lactational exposure routes. In general, the mouse pups were more vulnerable to ATZ toxicity than their mothers and exposure during gestation was suggested to be more effective than during lactation. The findings may support the need to further investigating the adverse effects of exposure to low doses of commonly used pesticides, especially during pregnancy and breast-feeding as well as effects on newborn child

THE PROTECTIVE EFFECT OF MORINGA TEA AGAINST CYPERMETHRIN-INDUCED HEPATORENAL DYSFUNCTION, OXIDATIVE STRESS, AND HISTOPATHOLOGICAL ALTERATIONS IN FEMALE RATS

Objectives: Exposure to α-cypermethrin (α-CP) may yield reactive oxygen species (ROS) that is responsible for oxidative stress in mammals. A variety of antioxidants were used to alleviate α-CP-induced toxicity in experimental animals. To the best of our knowledge, there are no attempts of using Moringa oleifera L. (MO) plant extracts against α-CP-induced toxicity. Therefore, this study was conducted.Methods: A total of 16 adult female rats were segregated into equally four groups: One group administered α-CP orally at a dose of 0.05/mg kg bw/ day; and the second group was freely allowed to drink MO leaf extract (moringa tea [MOT]) + the α-CP dose. The other two groups represented negative and positive controls. The daily consumption of the solutions was estimated. At the end of experiments (28 day), all animals were subjected to the planned manifestations.Results: MOT has proved its palatability as drinking solution more than water. Compared with control results, the relative weights of liver and brain recorded significant increases, while that of kidney, heart, spleen, ovary, and lung decreased significantly. Furthermore, alterations in the architecture of the liver, kidney, and brain were observed. α-CP treatment induced high elevation of the levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, creatinine, and malondialdehyde, while caused decline of butyrylcholinesterase, urea, superoxide dismutase, and total antioxidant capacity levels. Coadministration of MOT restored biochemical and histopathological alterations caused by α-CP to a great extent.Conclusion: The present study introduces novel data on the protective effect of MO leaf extract against CP toxicity and sheds light on the palatability of MOT†to rodents

In vivo antitumour potential of camel’s milk against hepatocellular carcinoma in rats and its improvement of cisplatin renal side effects

Context: Camel milk (CM) is recommended for liver disease patients in Egypt for a strong belief that it has a curative effect. Objective: The effect of consumption of CM with or without chemotherapeutic drug cisplatin was evaluated on induced hepatocarcinogenesis in rats. Materials and methods: Wistar male rats (56) were divided into eight groups (7 rats each). Group I was control. Hepatocarcinogenesis was initiated by a single dose of intraperitoneal injection of diethylnitrosamine (DENA) (200 mg/kg BW) and promoted by phenobarbitone (500 ppm) in drinking water in groups V, VI, VII and VIII. Treatment started from 28th till 38th week using CM (5 mL/day) and/or cisplatin (5 mg/kg/3 weeks) in groups II, III IV, VI, VII and VIII. Biochemical analysis, lipid peroxidation and superoxide dismutase (SOD) activity in liver tissue were performed. Histopathology of liver and kidney and immunohistochemistry of placental glutathione-S-transferase (P-GST) in liver were performed and analyzed using image analysis. Results: Albumin concentration and SOD activity were 3.13 ± 0.23 and 311.45 ± 41.71 in group VII (DENA & cisplatin), whereas they were 4.3 ± 0.15 and 540.5 ± 29.94 in group VII (DENA, CM and cisplatin). The mean area of altered hepatocellular foci and P-GST altered foci decreased in group VI (DENA and CM) (1049.6 ± 174.78 and 829.1 ± 261) and group VIII (cisplatin and CM) (1615.12 ± 436 and 543.9 ± 127) compared to group V (DENA only) (4173.74 ± 510.7 and 3169.49 ± 538.61). Cisplatin caused chronic interstitial nephritis, which was slightly alleviated in group VIII (CM and cisplatin). Conclusions: CM had an antioxidant effect and together with cisplatin managed to decrease hepatocarcinogenesis

Camel milk inhibits murine hepatic carcinogenesis, initiated by diethylnitrosamine and promoted by phenobarbitone

This study was carried out in order to investigate the possible inhibitory effect of camel milk (CM) on induced hepatocarcinogenesis in rats. Twenty-eight male rats were assigned into 4 groups (7 rats per group). Group I served as control negative. Group II treated with camel milk. Group III was injected I/P with diethylnitrosamine (DENA) (200 mg/kg) as a single dose and after one week received 500 ppm phenobarbitone in drinking water. Group IV injected with DENA as group III and treated with camel milk. Estimation of AST, ALT, albumin, total protein and alpha fetoprotein (AFP) in the serum of euthanized rats was performed. Histopathological examination and immunohistochemical staining of AFP and placental glutathione s transferase of the liver were carried out. Biochemical result at 38th week revealed an increase in serum AFP and a decrease in serum albumin on group III although no significance was detected. Histopathologically, the size of altered hepatic foci was smaller in the milk treated group (group IV). The number of mitotic figures observed in group IV was lower than group III. Hepatocellular carcinoma developed only in group III but not group IV. Immunohistochemical staining of AFP demonstrated an intense positive staining in group III and a weak positive staining in group IV. Similarly, the area percent of preneoplastic P-GST positive foci in liver was higher in group III than group IV. In conclusion, camel milk halted the progression of hepatocellular carcinoma

Zingerone Attenuates Carfilzomib-Induced Cardiotoxicity in Rats through Oxidative Stress and Inflammatory Cytokine Network

Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino rats. Rats were divided into five groups of six animals each. The first group received normal saline as a control (NC); the second group received multiple doses (six) of CFZ (4 mg/kg) intraperitoneally (IP); the third and fourth groups received zingerone (50 mg/kg and 100 mg/kg oral) along with six doses of CFZ for 16 days; and the fifth group received only 100 mg/kg zingerone orally. Hematological, biochemical, oxidative stress, and histopathological studies confirmed the findings of CFZ-induced cardiotoxicity. We found that ZRN significantly attenuated the effects of CFZ on oxidative stress by enhancing the antioxidant properties of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Additionally, ZRN reduces inflammatory cytokines and apoptotic markers, such as IL-1β, IL-6, TNFα, and caspase-3. Overall, zingerone prevents carfilzomib-induced cardiotoxicity in rats, as evidenced by histopathological studies

Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention

Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease’s development. To the best of our knowledge, no review articles have documented the intratumoral expression of CYPs and their implications in ovarian cancer. Therefore, the purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with the effects of CYP polymorphisms on chemotherapy metabolism. Finally, we discuss opportunities to exploit metabolic CYP expression for the development of novel therapeutic methods to treat ovarian cancer

Glypican-3 Differentiates Intraductal Carcinoma and Paget’s Disease from Other Types of Breast Cancer

Background and Objectives: breast cancer remains the most common health burden affecting females worldwide. Despite developments in breast cancer diagnostic approaches and treatment strategies, the clinical management of metastatic breast cancer remains challenging. Thus, there is a need to identify new biomarkers and novel drug targets for breast cancer diagnosis and therapy. Recently, aberrant glypican-3 (GPC3) expression in cancers has gained considerable interest in cancer research. The studies, however, have yielded contradictory results about GPC3 expression in breast cancer. Therefore, the current study aims to analyse GPC3 expression across a large panel of different breast cancer subtypes. Materials and Methods: GPC3 expression was immunohistochemically evaluated in 230 breast cancer patients along with eight normal tissues and its associations to clinical and demographic characteristics, as well as immunohistochemical biomarkers for breast cancer. Moreover, a public database consisting of breast cancer patients’ survival data and GPC3 gene expression information was used to assess the prognostic value of GPC3 in the survival of breast cancer patients. Results: GPC3 expression was only characterised in 7.5% of different histological breast cancer subtypes. None of the normal breast tissues displayed GPC3 expression. Interestingly, all cases of Paget’s disease, as well as 42.9% of intraductal and 16.7% of mucinous carcinomas were found to have GPC3 expression, where it was able to significantly discriminate Paget’s disease and intraductal carcinoma from other breast cancer subtypes. Importantly, GPC3 expression was found more often in tumours that tested positive for the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2), indicating more favourable histological subtypes of breast cancer. Consequently, longer relapse-free survival (RFS) was significantly correlated with higher GPC3 mRNA expression. Conclusions: Our study proposes that GPC3 is a promising breast cancer subtype-specific biomarker. Moreover, GPC3 may have the potential to be a molecular target for the development of new therapeutics for specific subtypes of breast cancer