Tirapazamine-Doxorubicin Interaction Referring to Heart Oxidative Stress and Ca2+ Balance Protein Levels

Doxorubicin (DOX) causes long-term cardiomyopathy that is dependent on oxidative stress and contractility disorders. Tirapazamine (TP), an experimental adjuvant drug, passes the same red-ox transformation as DOX. The aim of the study was to evaluate an effect of tirapazamine on oxidative stress, contractile protein level, and cardiomyocyte necrosis in rats administered doxorubicin. Rats were intraperitoneally injected six times once a week with tirapazamine in two doses, 5 (5TP) and 10 mg/kg (10TP), while doxorubicin was administered in dose 1.8 mg/kg (DOX). Subsequent two groups received both drugs simultaneously (5TP+DOX and 10TP+DOX). Tirapazamine reduced heart lipid peroxidation and normalised RyR2 protein level altered by doxorubicin. There were no significant changes in GSH/GSSG ratio, total glutathione, cTnI, AST, and SERCA2 level between DOX and TP+DOX groups. Cardiomyocyte necrosis was observed in groups 10TP and 10TP+DOX

Lepidium meyenii (Maca) – multidirectional health effects – review

Lepidium meyenii, commonly known as Maca, is a Peruvian plant that grows high in the Andes, in areas over 4,000 meters above sea level. Its composition contains almost all of the essential amino acids and twenty of the essential fatty acids needed by man, as well as many vitamins, minerals and several sterols and glucosinolates. The specific and unique unsaturated acids and amides found only in this plant are the macaenes and macamides. Most valuable ingredients are contained within the hypocotyls. Maca comes in three forms, based on its root colour, yellow, red and black. Although used individually, consumption recommendations are usually for a mix of all three. Since Inca times, it has been considered as super food

Risks associated with betel quid chewing

Betel quid is one of the most commonly used psychoactive substances in the world, especially among Asian communities, just after caffeine, nicotine and alcohol. The mixture that is chewed usually contains betel leaves, areca nut and slaked lime, nonetheless, its ingredients and the preparation manner tend to vary. Areca nut contains four main alkaloids - arecoline, arecaidyne, guvacine and guvacoline that are responsible for its psychoactive effects. The act of betel chewing might have a negative impact on an overall health and can cause pathological lesions or diseases to develop and/or progress, both directly and indirectly. Also, it may happen that the negative impact of betel chewing on one system might have indirect harmful influence on another. Still an association has been drawn between betel chewing and the presence of metabolic diseases, cancers and proteinuria, as well as cardiovascular disorders - including hypertension, chronic renal failure, diabetics type II and obesity. Likewise, it is a known risk factor in the development of oral and esophagus cancer. Moreover, a correlation between betel chewing and smoking exists in that betel chewing might theoretically hinder the abandonment of tobacco smoking. Tissues of oral cavity and the upper part of digestive system are additionally exposed to the mechanical injuries caused by the areca nut. Therefore, they tend to be the most prone to be pathologically affected by betel quid chewing

Autophagy in the pancreatic islets after the administration of cladribine in accordance to two different modes of therapy

The treatment of neoplastic and neurodegenerative diseases is still difficult. This because the cytostatic drugs have adverse effects on healthy organs. Among the drugs that have been investigated in the therapy of cancers and multiple sclerosis are the purine analogues. The aim of our study was the evaluation of the effect of cladribine on the process of autophagy in the healthy pancreas via two dosage models. The experiment was conducted on female Wistar rats which were placed within the experimental and control groups of two dosage models: model (A) - cladribine being administered in a daily dose of 0.1 mg/kg by weight for 7 days, and model (B) - cladribine being administered in a daily dose of 0.07 mg/kg by weight in 3 cycles of 6 days with 5 weeks break. A-bis and B-bis groups were included within, respectively, groups A and B. Here, decapitation occurred after 4 weeks break in drug administration. In our work, autophagy was investigated via the expression of the LC3B protein (Light Chain 3B protein). The comparison of the results of many independent trials was built upon the use of the Kruskal-Wallis non-parametric test. Significance was set at p < 0.005. In our results, average LC3B expression was observed in 100% of all cells in the group A, 70% in group B and 60% in group B-bis. We not observed average LC3B expression in the other groups. Moreover, a poor reaction was observed in 55% of all cells in group A-bis. We noted significant relationships between control group and group A, between the control group and group B, and between group A-bis and groups B and B-bis. These results demonstrate that cladribine has led to the induction of autophagy in the pancreatic islet cells

Apoptosis of rats’ cardiomyocytes after chronic energy drinks consumption

Energy drinks (ED) are beverages containing caffeine, taurine, vitamins, herbal extracts, and sugar or sweeteners. They are marketed as capable of improving stamina, athletic performance and concentration, moreover, as serving as a source of energy. Still, there are very few papers describing the impact of ED on cell biology – including cell apoptosis within tissues. Therefore, in our study, we assessed the symptoms of rat cardiomyocytes apoptosis after 8 weeks consumption of ED

A comparison of caspase 3 expression in the endocrine and exocrine parts of the pancreas after cladribine application according to the "leukemic" schema

The therapeutic effects of the immunosuppressive agent, cladribine, have been demonstrated by its toxicity to cells. However, its effects on healthy cells of the body is poorly understood. The aim of study was, hence, to, firstly, evaluate the morphology of the endocrine and exocrine pancreas after the administration of cladribine according to the "leukemic" schema, and, secondly, to assess its impact on the intensity of apoptosis. The experiment was carried out on female Wistar rats which were placed within the control group KA, and the experimental groups: A and A-bis. In the experimental groups, Cladribine was administered according to the cycle used to treat human hairy cell leukemia. In group A, the material was taken 24 hours after administration of the last dose of the drug, while in group A-bis, this was done after a 4 weeks break. The reaction was assessed to be average in 80% of all cells in group A, and in 64% of all acinar cells in group KA, while in group A-bis, the majority of the exocrine cells demonstrated a lack of immunohistochemical response (72%). Moreover, most endocrine cells (60%) in group A-bis revealed a strong reaction, while in Group A, the corresponding figure is a little over 34%. A comparison of the severity of the caspase 3 expression in both the exocrine and endocrine pancreas showed significant differentiation results between the group KA and group A-bis, and between group A and A-bis (p < 0.0001). In can be concluded that endocrine cells are more sensitive to cladribine than are exocrine cells

Intensification of Doxorubicin-Related Oxidative Stress in the Heart by Hypothyroidism Is Not Related to the Expression of Cytochrome P450 NADPH-Reductase and Inducible Nitric Oxide Synthase, As Well As Activity of Xanthine Oxidase

Cytochrome P450 NADPH-reductase (P450R), inducible synthase (iNOS) and xanthine oxidase play an important role in the antracycline-related cardiotoxicity. The expression of P450R and iNOS is regulated by triiodothyronine. The aim of this study was to evaluate the effect of methimazole-induced hypothyreosis on oxidative stress secondary to doxorubicin administration. 48 hours after methimazole giving cessation, rats were exposed to doxorubicin (2.0, 5.0 and 15 mg/kg). Blood and heart were collected 4, 48 and 96 h after the drug administration. Animals exposed exclusively to doxorubicin or untreated ones were also assessed. The hypothyreosis (0.025% of methimazole) significantly increased the doxorubicin effect on the cardiac carbonyl group and they may increase the glutathione level. An insignificant effect of methimazole was noticed in case of the cardiac lipid peroxidation product, the amount of DNA oxidative damages, iNOS and xanthine oxidase-enzymes responsible for red-ox activation of doxorubicin. However, the concentration of P450R was affected by a lower dose of methimazole in rats administered with doxorubicin. Since in rats receiving doxorubicin changes in oxidative stress caused by methimazole were not accompanied by elevation of bioreductive enzymes, it may be concluded that these changes in the oxidative stress were not related to the tested enzymes

The differential effects of green tea on dose-dependent doxorubicin toxicity

Background: Doxorubicin (DOX) is an anticancer drug displaying cardiac and hepatic adverse effects mostly dependent on oxidative stress. Green tea (GT) has been reported to play a protective role in diseases resulting from oxidative stress. Objective: The objective of this study was to evaluate if GT protects against DOX-induced oxidative stress, heart and liver morphological changes, and metabolic disorders. Methods: Male Wistar rats received intraperitoneal injection of DOX (1.0 or 2.0 mg/kg b.w.) for 7 weeks or concomitantly GT extract soluble in drinking water. Results: There were multidirectional effects of GT on blood metabolic parameters changed by DOX. Among all tested biochemical parameters, statistically significant protection of GT against DOX-induced changes was revealed in case of blood fatty acid–binding protein, brain natriuretic peptide, and superoxide dismutase. Conclusion: DOX caused oxidative stress in both organs. It was inhibited by GT in the heart but remained unchanged in the liver. DOX-induced general toxicity and histopathological changes in the heart and in the liver were mitigated by GT at a higher dose of DOX and augmented in rats treated with a lower dose of the drug