Background: One of the most important causative agents of visceral leishmaniasis (VL) is Leishmania infantum, which is mainly spread by Phlebotomus and Lutzomyia sandflies in the Old and New World, respectively. Novel and effective drugs to manage this neglected vector-borne disease are urgently required. In this study, we evaluated the toxicity of carvacrol, thymol and linalool, three common essential oil constituents, on amastigotes and promastigotes of L. infantum. Methods: in vitro experiments were performed by 24 h MTT assay. Carvacrol, thymol and linalool at concentrations ranging from 1.3 to 10 μg/mL were tested on promastigotes of L. infantum. For in vivo test, two groups of hamsters (Mesocricetus auratus) received 100 mg/kg of body weight/day of carvacrol and thymol as intraperitoneal injection on day 7 post-infection, followed by a 48 h later injection. The third group was treated with the glucantime as standard drug (500 mg/kg) and the last group (control) just received normal saline. On the 16th day, the number of parasites and histopathological changes in liver and spleen were investigated. Results: 24 h MTT assay showed promising antileishmanial activity of thymol and carvacrol, with IC₅₀ values of 7.2 (48 μM) and 9.8 μg/mL (65 μM), respectively. Linalool at all concentrations did not affect L. infantum promastigote viability. In vivo toxicity data of carvacrol and thymol showed that the former at 100 mg/kg was the safest and most effective treatment with little side effects on the liver. Conclusions: Overall, thymol and carvacrol are highly promising candidates for the development of effective and safe drugs in the fight against VL.

Background and Objective. 5‐Fluorouracil is one of the most common chemotherapeutic agents used in the treatment of solid tumors. 5‐Fluorouracil‐associated cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Colchicine is a strong anti‐inflammatory drug used to prevent and treat acute gout and treat familial Mediterranean fever. And also, its protective effects on cardiovascular disease have been reported in various studies. The current study is aimed at appraising the effect of colchicine on 5‐fluorouracil‐induced cardiotoxicity in rats. Methods. Twenty male Wistar rats were divided into four groups as follows: control, 5‐fluorouracil, colchicine (5 mg/kg), and 5‐fluorouracil+5 mg/kg colchicine. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5‐fluorouracil (100 mg/kg). The control group received normal saline, and the treatment groups received colchicine with an intraperitoneal injection for 14 days. Findings. 5‐Fluorouracil resulted in significant cardiotoxicity represented by an increase in cardiac enzymes, malondialdehyde levels, cyclooxygenase‐2 and tumor necrosis factor‐alpha expression, cardiac enzymes, and histopathological degenerations. 5‐Fluorouracil treatment also decreased body weight, total antioxidant capacity and catalase values, blood cells, and hemoglobin levels. In addition, 5‐fluorouracil disrupted electrocardiographic parameters, including increased elevation in the ST segment and increased QRS duration. Treatment with colchicine reduced oxidative stress, cardiac enzymes, histopathological degenerations, and cyclooxygenase‐2 expression in cardiac tissue, improved electrocardiographic disorders, and enhanced the number of blood cells and total antioxidant capacity levels. Moreover, body weight loss was hampered after treatment with colchicine. Our results demonstrated that treatment with colchicine significantly improved cardiotoxicity induced by 5‐fluorouracil in rats.

Background. Fluorouracil (5‐FU) is the third most common chemotherapeutic agent used in the treatment of solid tumors. 5‐FU‐associated cardiotoxicity ranks the second causes of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Kaempferol (KPF), a common flavonoid, possessing anti‐inflammatory, antiapoptotic, antioxidative properties, and its protective effects on cardiovascular disease has been reported in various studies. The current study is aimed at appraising the effect of KPF and KPF nanoparticles (NPs) on 5‐FU‐induced cardiotoxicity in rats. Methods. Thirty Male Wistar rats were divided into five groups as follows: control, 5‐FU, 5‐FU+10 mg/kg vitamin C, 5‐FU+ 1 mg/kg KPF, and 5‐FU+ 1 mg/kg KPF‐NPs. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5‐FU (100 mg/kg). The control group received normal saline, and the treatment groups received KPF and KPF‐NPs with an intraperitoneal injection for 14 days. Each heart histopathological lesions were given a score of 0 to 3 in compliance with the articles for statistical analysis. Results. 5‐FU resulted in a significant cardiotoxicity represented by an increase in cardiac enzymes, MDA (malondialdehyde) levels, COX‐2 (cyclooxygenase‐2) expression, and histopathological degenerations. 5‐FU treatment also decreased body weight, TAC (total antioxidant capacity) values, VEGF (vascular endothelial growth factor) expression, blood cells, and hemoglobin (Hb) levels. Treatment with KPF and KPF‐NPs reduced oxidative stress, cardiac enzymes, COX‐2 expression, and VEGF expression. The number of blood cells, Hb levels, and histopathological degenerations, in cardiac tissue also body weight of animals, increased, followed by treatment with KPF and KPF‐NPs. Conclusion. Our results demonstrated that treatment with KPF and KPF‐NPs significantly improved cardiotoxicity induced by 5‐FU in rats.

Propolis is a natural compound with anticarcinogenic properties. The present study aimed to compare the inhibitory effect of ethanolic extract of propolis (EEP) and vitamin E on dimethylhydrazine‐induced colon lesions in rats. In this study, 60 rats were randomly categorized into six 10‐member groups. After 13 weeks, blood and colon tissue were sampled to examine some factors. The parameters included red (RBC) and white (WBC) blood cell profile, lactate dehydrogenase (LDH), C‐reactive protein (CRP), total protein (TP), creatine kinase (CPK), and albumin, as well as the extent of colon histological lesions, protein expression (adenomatous polyposis coli (APC), proliferating cell nuclear antigen (PCNA), carcinoembryonic antigen (CEA), and platelet‐derived growth factor (PDGF)), and oxidative stress markers (total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD)) in colon tissue. A significant decrease was observed in congestion, mitotic index, inflammation, and cell destruction in colon tissue in dimethylhydrazine group in comparison with the control group (P < 0.05). The EEP exposed rats exhibited a significant lower oxidative stress than the DMH group (P < 0.05). Furthermore, the extract significantly affected TAC level (P < 0.05). While the expression level of APC rose substantially in the EEP‐treated group compared to the DMH group, the level of PCNA, CEA, and PDGF proteins significantly reduced. It seems that the EEP can efficiently prevent DMH‐induced colonic lesions. Furthermore, its effectiveness is more than the vitamin E, which is a strong antioxidant.