Cisplatin (CP) has been used in wide range for cancer treatment. Although nephrotoxicity of CP was the main complication, cardiotoxicity has been reported. This study investigates the protective role of green tea extract (GTE) and vitamin E (Vit-E) against CP-induced cardiotoxicity, and assesses their impact on CP antitumor efficacy. Forty-eight male albino Balb/c mice were randomly divided into six groups, 8 per/group (Gp) were included. Gp1 served as control; Gp2 and Gp3 received oral GTE (400 mg/kg) and Vit-E (100 mg/kg) for 30 consecutive days respectively. Gp4 had received CP (7 mg/kg i.p.) once on the 27th day; Gp5 had received GTE (400 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Gp6 had received Vit-E (100 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Blood and tissues samples were harvested for biochemical and histopathological investigations. To evaluate the effect of GTE and Vit-E on the antitumor efficacy of CP, 49 female albino mice were inoculated intraperitoneally by Ehrlich ascetic carcinoma -cells (2 × 10⁶/mouse) then treated with none, corn oil, CP, CP/GTE, CP/Vit-E, GTE or Vit-E. CP injection significantly increased Troponin I, CPK, CK-MB, malondialdehyde (MDA), and nitric oxide (NO) levels, while glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase levels were significantly reduced with disruption of cardiac muscle fibers, loss of striations, absence of intercalated disc, and the nuclei are pyknotic. Treatment with GTE and Vit-E improve the biochemical and histological parameters. Treatment with CP alone led to eradication of the tumor cells from the tumor-bearing mice. However, co-administration of GTE or Vit-E orally with CP did not interfere with its therapeutic effects. Treatment with GTE and Vit-E significantly ameliorated the CP cardiotoxicity and improved the myocardial histopathological architecture. GTE and Vit-E may be combined with CP to alleviate cardiotoxicity in cancer chemotherapy without interfering with its antitumor activity.

Background: the nephrotoxicity of methotrexate (MTX) is observed in high-dose therapy. Moreover, low-dose MTX therapy for rheumatic diseases is debatable and claimed to cause renal impairment. This study aimed at studying the effect of methotrexate in repeated low doses on rat kidneys and assessing the efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) and platelet rich plasma (PRP) for attenuating this effect. Methods: Forty-two male Wistar rats were used, 10 rats were donors of AD-MSCs and PRP, 8 rats served as control, and the remaining rats were subjected to induction of nephrotoxicity by MTX intraperitoneal injection once weekly for successive 8 weeks and then assigned into 3 groups of 8 animals each: Group II: received MTX only. Group III: received MTX + PRP. Group IV: received MTX + AD-MSCs. After one month, rats were anaesthetized, serum-sampled, and renal tissue removed for biochemical, histological, and ultrastructural evaluation. Results: there was significant tubular degeneration, glomerulosclerosis, fibrosis, decreased renal index, along with increased levels of urea and creatinine in the MTX group compared to the control group. Immunohistochemical expression of caspase-3 and iNOS in the renal tissue was significantly increased in group II compared to groups III and IV. Biochemical results revealed higher tissue malondialdehyde (MDA) concentration in the MTX-injected group which decreased significantly in co-treatment with either AD-MSC or PRP + MTX. MSC promoted the activation of the Nrf2/PPARγ/HO-1 and NF-κB/Keap1/caspase-3 pathways, increased antioxidant enzyme activities, reduced lipid peroxidation levels, and alleviated oxidative damage and apoptosis. PRP showed therapeutic effects and molecular mechanisms similar to MSC. Furthermore, MSC and PRP treatment significantly reduced MTX-induced upregulation of the pro-inflammatory (NF-κB, interleukin-1ß, and TNF-α), oxidative stress (Nrf-2, hemoxygenase-1, glutathione, and malondialdehyde), and nitrosative stress (iNOS) markers in the kidney. Conclusion: repeated administration of low-dose MTX resulted in massive renal tissue toxicity and deterioration of renal function in rats which proved to be attenuated by PRP and AD-MSCs through their anti-inflammatory, anti-apoptotic and anti-fibrotic properties.

Drug-induced cardiotoxicity is a major adverse effect that has been encountered for some clinically important drugs especially antineoplastic agents. This toxicity has previously led to the post-marketing withdrawal of numerous pharmacologically active drugs and limits the efficacy of other clinically useful ones. Currently, assessing the cardiotoxicity potential is a crucial parameter in drug development, and many models have been established to facilitate its prediction to avoid such toxicity. In this chapter, we will briefly discuss the mechanism of drug-induced cardiotoxicity, risk factors, how to prevent, early detection and/or management from a pharmacological and toxicological point of view.

The organophosphorus (OP) pesticide malathion is a highly neurotoxic compound, leading to cholinergic syndrome. Malathion produces reproductive toxicity. To investigate the protective effects of curcumin on the testicular toxicity induced in male mice orally administrated with malathion. Forty-eight mature male mice were used. The mice were divided into four groups, 12 mice each, and treated for 4 weeks as follows: the control (G1), curcumin-treated group (G2), malathion-treated group (G3), and the curcumin plus malathion-treated group (G4). At the end of the experiment, the mice were sacrificed and dissected, and tissue samples were obtained and antioxidant parameters were examined. Tissue samples were also histopathologicaly and immunohistochemically assessed. Samples of blood were collected for assessing the levels of serum hormones, namely follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and acetylcholinesterase activity (AChE). Malathion exposure caused a decrease in serum testosterone and LH levels and antioxidant enzymes (SOD and CAT) and elevation of oxidative stress marker (MDA). Histological changes were as well observed in the form of maturation abnormalities, intratubular necrosis, and inflammatory infiltrate in malathion-treated mice. Co-administration of curcumin with malathion reduced lipid peroxidation (LPO) activity and improved spermatogenesis and increased catalase (CAT), superoxide dismutase (SOD), and testosterone levels. The current study showed that curcumin could ameliorate the elevated concentration of lipid peroxidation products, increase the levels of antioxidative markers, and improve the pathological changes in the testis induced by malathion administration. The capacity of curcumin to work as antioxidant supposedly relates to its structure.

Nsions in Saudi population. Subjects and Methods: Three hundred and fifty participants in 20–30 years' age group were incorporated into a cross-sectional study. The research population included 150 males and 150 females as a study group, and 50 participants as a control group to test the accuracy of the formulae. Nine measurements of different hand dimensions (hand length, palm length, handbreadth, maximum handbreadth, and five phalanges lengths) and statures were taken. The simple linear regression equations and multiple linear regression equations with the explanatory variables were suggested as a statistical model to clarify the total variation in stature. Results: Statistical analysis indicated that the bilateral variations were insignificant for all the measurements (P > 0.05). The correlation between the stature and different parameters studied in males and females were found to be positive and statistically highly significant (P < 0.001). The highest correlation with stature was observed with hand length and palm length than the other variables. Linear and multiple regression equation for stature estimation were calculated separately for males and females. The derived equations were applied to the control group, and it was noticed that the percentage difference between true stature of the control and the estimated stature ranged from 0.01% to 0.12%. The multiple linear regression equation was more reliable than the simple linear regression equations. Conclusion: The findings of the present study have provided the regression equations from hand dimensions that can be used for predicting stature of adult Saudi population....