Mild histological distortions in rat organs after a 14-day oral exposure to the slime extract of African giant land snails.

Objective: Snail slime possesses various pharmacological activities that are becoming attractive for zootherapy, thereby necessitating the profiling of its safety and toxicity. Therefore, using OECD 425 guidelines, this study assessed the acute toxicity of Archachatina marginata slime extract and performed a histological analysis of the vital organs. Methods: Eighteen (18) Wistar rats were assigned randomly into three groups: control, 2000 mg/kg, and 5000 mg/kg bw slime extract. The dosing of the animals with 2000 mg/kg bw and 5000 mg/kg bw was done according to the limit test procedure, after which the animals were observed for 14 days. During the observation period, clinical and behavioral changes were recorded. The rats were euthanized after 14 days of monitoring, and their essential organs were excised for gross histological examination. Results: There was no mortality during the observation period, and the LD50 of A. marginata slime extract was determined to be greater than 5000 mg/kg bw. Although there were no behavioral alterations in the rats after oral exposure to the slime extract, the histological examination revealed mild cellular distortions in the rat organs. Furthermore, a preliminary chemical analysis of the slime extract revealed the presence of flavonoids and phenolics. Conclusion: A. marginata slime extracts may be grouped as low toxic substance based on the results obtained (LD50 > 2000 - 5000 mg/kg). However, the histological distortions in rat organs following acute oral exposure to the snail slime extract not only warrant further, in-depth toxicological investigations but also caution in its use for traditional medicinal purposes.

Reassessing vascular endothelial growth factor (VEGF) in anti-angiogenic cancer therapy.

Vascularization is fundamental to the growth and spread of tumor cells to distant sites. As a consequence, angiogenesis, the sprouting of new blood vessels from existing ones, is a characteristic trait of cancer. In 1971, Judah Folkman postulated that tumour growth is angiogenesis dependent and that by cutting off blood supply, a neoplastic lesion could be potentially starved into remission. Decades of research have been devoted to understanding the role that vascular endothelial growth factor (VEGF) plays in tumor angiogenesis, and it has been identified as a significant pro-angiogenic factor that is frequently overexpressed within a tumor mass. Today, anti-VEGF drugs such as Sunitinib, Sorafenib, Axitinib, Tanibirumab, and Ramucirumab have been approved for the treatment of advanced and metastatic cancers. However, anti-angiogenic therapy has turned out to be more complex than originally thought. The failure of this therapeutic option calls for a reevaluation of VEGF as the major target in anti-angiogenic cancer therapy. The call for reassessment is based on two rationales: first, tumour blood vessels are abnormal, disorganized, and leaky; this not only prevents optimal drug delivery but it also promotes hypoxia and metastasis; secondly, tumour growth or regrowth might be blood vessel dependent and not angiogenesis dependent as tumour cells can acquire blood vessels via non-angiogenic mechanisms. Therefore, a critical assessment of VEGF, VEGFRs, and their inhibitors could glean newer options such as repurposing anti-VEGF drugs as vascular normalizing agents to enhance drug delivery of immune checkpoint inhibitors.

Combine effect of exposure to petrol, kerosene and diesel fumes: On hepatic oxidative stress and haematological function in rats.

Petroleum product fumes (PPFs) containing toxic organic components are pervasive in the environment, emanating from anthropogenic activities, including petroleum exploration and utilization by end-user activities from petrol-gasoline stations. Petrol station attendants are exposed to PPF through inhalation and dermal contact with consequent toxicological implications. We investigated the effects of chronic exposure (60 and 90 days) to petrol (P), kerosene (K) and diesel (D) alone and combined exposure to petrol, kerosene and diesel (PKD) fumes on hepatotoxicity, haematological function and oxidative stress in rats. Following sacrifice, we evaluated hepatic damage biomarkers, blood glucose, oxidative stress and haematological function. Chronic exposure to PPF significantly increased organo-somatic indices, blood glucose, biomarkers of hepatic toxicity and oxidative stress in an exposure duration-dependent manner. There was a simultaneous decrease in the protective capacity of antioxidants. Furthermore, exposure to PPF increased pro-inflammatory biomarkers in rats (90 > 60 days). Regardless of exposure duration, plateletcrit, mean platelet volume, platelet distribution width and red cell distribution width in the coefficient of variation increased, whereas red blood cell count, haemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, white blood cell, lymphocyte, monocyte-basophil-eosinophil mixed counts and platelet count decreased after 60 and 90 days exposure. Microscopic examination of the liver demonstrated hepatic pathological changes paralleling the duration of exposure to PKD fumes. However, the injury observed was lesser to that of rats treated with the diethylnitrosamine - positive control. Our results expanded previous findings and further demonstrated the probable adverse effect on populations' health occasioned by persistent exposure to PPF. Individuals chronically exposed by occupation to PPF may be at greater risk of developing disorders promoted by continuous oxido-inflammatory perturbation and suboptimal haematological-immunologic function - thereby enabling a permissive environment for pathogenesis notwithstanding the limitation of quantifying PPF absolute values in our model system.

Oxido-inflammatory responses and histological alterations in rat lungs exposed to petroleum product fumes.

Petroleum products-petrol, kerosene, and diesel-composed of volatile organic constituents contribute to air pollution. Exposure of gas station attendants (GSAs) to petroleum products fumes (PPFs) may account for occupation-related predisposition to respiratory toxicity and disease pathogenesis. We simulated GSA exposure to PPF inhalation and examined their effect on oxido-inflammatory responses, toxicity, and histopathological alterations in rat lungs, following 8-hours daily exposure for 60 and 90 days. Reactive oxygen and nitrogen species (RONS), oxidative stress and inflammatory biomarkers, namely: superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), TNF-α, IL-1ß, xanthine oxidase (XO), nitric oxide (NO) activity were evaluated. Besides, histopathological examination of the lungs and trachea of exposed rats, PPF exposure resulted in significant (P < .05) increases in RONS, biomarkers of oxidative stress, pro-inflammation cytokines, and reduced (P < .05) GSH levels in rats, secondary to histopathological alteration in lungs and trachea cytoarchitecture examined in an exposure-duration-dependent manner. We conclude, therefore, that the observed biochemical and histological changes create a microenvironment that is permissive to diseases pathogenesis of the respiratory system via oxido-inflammatory mechanistic pathways.