Protective effects of macromolecular polyphenols, metals (zinc, selenium, and copper) - Polyphenol complexes, and different organs with an emphasis on arsenic poisoning: A review.

For the potential health benefits and nutritional value, polyphenols are one of the secondary metabolites of plants that have received extensive research. It has anti-inflammatory and cytotoxicity-reducing properties in addition to a high antioxidant content. Macromolecular polyphenols and polysaccharides are biologically active natural polymers with antioxidant and anti-inflammatory potential. Arsenic is an ecologically toxic metalloid. Arsenic in drinking water is the most common way people come into contact with this metalloid. While arsenic is known to cause cancer, it is also used to treat acute promyelocytic leukemia (APL). The treatment's effectiveness is hampered by the adverse effects it can cause on the body. Oxidative stress, inflammation, and the inability to regulate cell death cause the most adverse effects. Polyphenols and other macromolecules like polysaccharides act as neuroprotectants by mitigating free radical damage, inhibiting nitric oxide (NO) production, lowering A42 fibril formation, boosting antioxidant levels, and controlling apoptosis and inflammation. To prevent the harmful effects of toxins, polyphenols and pectin lower oxidative stress, boost antioxidant levels, improve mitochondrial function, control apoptosis, and suppress inflammation. Therefore, it prevents damage to the heart, liver, kidneys, and reproductive system. This review aims to identify the effects of the polyphenols in conjugation with polysaccharides as an ameliorative strategy for arsenic-induced toxicity in various organs.

Molecular Crosstalk between the Immunological Mechanism of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Oral Cancer.

Oral cancer is a significant non-communicable disease affecting both emergent nations and developed countries. Squamous cell carcinoma of the head and neck represent the eight major familiar cancer types worldwide, accounting for more than 350,000 established cases every year. Oral cancer is one of the most exigent tumors to control and treat. The survival rate of oral cancer is poor due to local invasion along with recurrent lymph node metastasis. The tumor microenvironment contains a different population of cells, such as fibroblasts associated with cancer, immune-infiltrating cells, and other extracellular matrix non-components. Metastasis in a primary site is mainly due to multifaceted progression known as epithelial-to-mesenchymal transition (EMT). For the period of EMT, epithelial cells acquire mesenchymal cell functional and structural characteristics, which lead to cell migration enhancement and promotion of the dissemination of tumor cells. The present review links the tumor microenvironment and the role of EMT in inflammation, transcriptional factors, receptor involvement, microRNA, and other signaling events. It would, in turn, help to better understand the mechanism behind the tumor microenvironment and EMT during oral cancer.

Exploring the Pattern of Metabolic Alterations Causing Energy Imbalance via PPARα Dysregulation in Cardiac Muscle During Doxorubicin Treatment.

Cardiotoxicity by anthracycline antineoplastic drug doxorubicin is one of the systemic toxicity of the cardiovascular system. The mechanism responsible for doxorubicin cardiotoxicity and lipid metabolism remains elusive. The current study tested the hypotheses that the role of peroxisome proliferator-activated receptor α (PPARα) in the progress of doxorubicin-induced cardiomyopathy and its mechanism behind lipid metabolism. In the present study, male rats were subjected to intraperitoneal injection (5-week period) of doxorubicin with different dosages such as low dosage (1.5 mg/kg body weight) and high dosage (15 mg/kg body weight) to induce doxorubicin cardiomyopathy. Myocardial PPARα was impaired in both low dosage and high dosage of doxorubicin-treated rats in a dose-dependent manner. The attenuated level of PPARα impairs the expression of the genes involved in mitochondrial transporter, fatty acid transportation, lipolysis, lipid metabolism, and fatty acid oxidation. Moreover, it disturbs the reverse triacylglycerol transporter apolipoprotein B-100 (APOB) in the myocardium. Doxorubicin elevates the circulatory lipid profile and glucose. Further aggravated lipid profile in circulation impedes the metabolism of lipid in cardiac tissue, which causes a lipotoxic condition in the heart and subsequently associated disease for the period of doxorubicin treatment. Elevated lipids in the circulation translocate into the heart dysregulates lipid metabolism in the heart, which causes augmented oxidative stress and necro-apoptosis and mediates lipotoxic conditions. This finding determines the mechanistic role of doxorubicin-disturbed lipid metabolism via PPARα, which leads to cardiac dysfunction.

Review on molecular and biochemical insights of arsenic-mediated male reproductive toxicity.

Arsenic is a natural metalloid found in abundance, in the environment. Exposure to arsenic can cause health issues due to its carcinogenic nature. The primary source of arsenic contact is drinking water. Exposure to arsenic in drinking water can cause reproductive dysfunction in males through a reduction in testes weight, accessory sex organ weight, viability, and motility of sperm, epididymal sperm count, decreased gonadotrophins level, decreased testosterone, and steroidogenesis disruption. This review focuses on the mechanisms by which arsenic impairs the quality of semen, based on epidemiological observations in humans, and experimental studies in different biological research models. Arsenic-mediated male reproductive toxicity can be induced by various mechanisms such as inhibition of spermatogenesis, testosterone pathway hinderance, oxidative stress, inflammation, genotoxic effects, activation of heat shock proteins, and activation of a signaling pathway in testes (ERK/AKT/NF-kB signaling pathway), among others. The interplay between the principal mechanisms involved needs to be elucidated further in future since an overall examination of arsenic-mediated male reproductive toxicity is still a deficit.