Ocular surface and chronic pesticide exposure: Evaluating the alterations in corneal cellular turnover concerning cell cycle and apoptosis.

The consequences of chronic pesticide exposure on the ocular surface are not yet fully known and lacunae exist regarding the repercussions of this xenobiotic insult on cellular turnover. The present work aims to establish the mechanistic relationship between ocular morbidity and chronic pesticide exposure by analyzing the impact on key regulators responsible for cell cycle and death. Vital components of cell cycle and death were primarily explored in this study by mimicking the on-field scenario regarding chronic pesticide exposure in a murine model. Various cellular aspects were taken into consideration through culture analyses, flowcytometric evaluation, fluorescence microscopic studies etc. We observed downregulation of key players of the cell-cycle at different stages (viz. Cyclin-D1, CDK4, pRb, PCNA, PP1, PP2A, p-cdc 25c and Aurora kinase A) with a corresponding increase in the expression of cell-cycle inhibitors like p18 and p21, which lead to hypoproliferation of corneal epithelial cells post pesticide exposure. The expression of GSK 3ß, a master-molecule involved in both cell cycle and apoptotic pathways corresponded well with the scientific theme and indicated towards cellular hypoproliferation and increase of apoptosis. Key players of both the intrinsic (viz. Bax/Bcl2, JNK) and extrinsic (viz. CD 95) apoptotic pathways were found to be activated leading to enhanced cleaved Caspase 3 expression and corresponding cell death. We tried to highlight the mechanistic correlation between the alterations in cellular turnover as the reason behind the heightened ocular morbidity due to 'chronic pesticide exposure'- the xenobiotic stress exerted by these 'farmers' friends'.

Therapeutic management of peritoneal ascitic sarcomatosis by Ruta graveolens: A study in experimental mice.

RELEVANCE: Malignant peritoneal sarcomatosis related ascitic formation often leads to grave consequences but the therapeutic management of the fatal pathophysiological condition remains a rarely discussed issue. The present study investigates the anti-neoplastic activity of the plant alkaloid from Ruta graveolens on ascitic Sarcoma-180 bearing mice as a model of human malignant peritoneal ascites. MATERIALS AND METHODS: The efficacy of the loco-regional administration of Ruta graveolens on tumour cells was explored with cytopathological and cytotoxicological studies, along with the expressional modulation vital regulatory molecules viz. Chk2, c-Myc, CD95 and Aurora kinase. RESULTS: The study revealed a series of anti-neoplastic events exerted by Ruta graveolens that included the boosting of anti-tumour immunity, generation of tumour cell cytotoxicity and disruption of cellular energetics which lead to the induction of apoptosis and simultaneous impairment of cell division in tumour cells. Expressional decline of c-Myc oncoproteins and mitosis promoter Aurora kinase A together with up regulation of vital tumour suppressor Chk-2 and apoptosis inducer CD 95 in ascitic tumour cells was also found to be associated with Ruta administration. CONCLUSION: Our observations revealed that loco-regional Ruta administration resulted in the anti-neoplastic effect on peritoneal sarcoma related ascites and the alteration of vital regulatory molecules which depicted the therapeutic utility of Ruta in the management of peritoneal malignant ascites.

Chronic pesticide exposure and consequential keratectasia & corneal neovascularisation.

Ocular toxicity as a consequence of chronic pesticide exposure is one of the health hazards caused due to extended exposure to pesticides. The cornea, due to its position as the outer ocular layer and its role in protecting the internal layers of the eye; is gravely affected by this xenobiotic insult to the eye, leading to ocular irritation and damage to normal vision. The deleterious effects of chronic pesticide exposure on the various corneal layers and the ocular risks involved therein, were explored by mimicking the on-field scenario. Cytological, histological and flowcytometric parameters were taken into consideration to determine the enhanced risk of corneal neovascularisation and keratectasia, specifically, keratoconus. Chronic exposure to pesticides leads to heightened ocular morbidity wherein there were visible pathophysiological changes to the ocular surface. The cornea was found to be adversely affected with visible protuberance in a cone-like shape, characteristic of keratoconus in a majority of the experimental animals. Further analyses revealed a detrimental impact on all the corneal layers and an amplified expression of inflammation markers such as TNF-α, VCAM-1 and ICAM-1. Additionally, it was found that post pesticide exposure, the corneal surface developed hypoxia, leading to a significant increase of angiogenesis promoting factors and consequential neovascularisation. Apart from ocular toxicity, chronic exposure to pesticides significantly increases the risks of keratectasia and corneal neovascularisation; disorders which lead to diminished vision and if untreated, blindness.