Investigating the therapeutic potential of Allium cepa extract in combating pesticide exposure induced ocular damage.

The ocular surface is subject to a range of potentially hazardous environmental factors and substances, owing to its anatomical location, sensitivity, and physiological makeup. Xenobiotic stress exerted by chronic pesticide exposure on the cornea is primarily responsible for ocular irritation, excessive tear production (hyper-lacrimation), corneal abrasions and decreased visual acuity. Traditional medicine hails the humble onion (Allium cepa) for its multi-faceted properties including but not limited to anti-microbial, antioxidant, anti-inflammatory and wound healing. However, there is a lacuna regarding its impact on the ocular surface. Thereby, the current study investigated whether topical application of crude extract of Allium cepa aided in mitigating pesticide-induced damage to the ocular surface. The deleterious effects of pesticide exposure and their mitigation through the topical application of herbal extract of Allium cepa were analysed initially through in vitro evaluation on cell lines and then on the ocular surface via various in-vivo and ex-vivo techniques. Pathophysiological alterations to the ocular surface that impacted vision were explored through detailed neurophysiological screening with special emphasis on visual acuity wherein it was observed that the murine group treated with topical application of Allium cepa extract had comparable visual capacity to the non-pesticide exposed group. Additionally, SOD2 was utilized as an oxidative stress marker along with the expression of cellular apoptotic markers such as Bcl-xL to analyse the impact of pesticide exposure and subsequent herbal intervention on oxidative stress-induced corneal damage. The impact on the corneal epithelial progenitor cell population (ABCG2 and TERT positive cells) was also flowcytometrically analysed. Therefore, from our observations, it can be postulated that the topical application of Allium cepa extract might serve as an effective strategy to alleviate pesticide exposure related ocular damage.

Mitigation of pesticide-mediated ocular toxicity via nanotechnology-based contact lenses: a review.

The xenobiotic stress exerted by pesticides leads to the deterioration of human and animal health including ocular health. Acute or prolonged exposure to these agricultural toxicants has been implicated in a number of pathological conditions of the eye such as irritation, epiphora or hyper-lacrimation, abrasions on the ocular surface, and decreased visual acuity. The issue is compounded by the fact that tissues of the eye absorb pesticides faster than other organs of the body and are more susceptible to damage as well. However, there is a lacuna in our knowledge regarding the ways by which pesticide exposure-mediated ocular insult might be counteracted. Topical instillation of drugs known to combat the pesticide induced toxicity has been explored to mitigate the detrimental impact of pesticide exposure. However, topical eye drop solutions exhibit very low bioavailability and limited drug residence duration in the tear film decreasing their efficacy. Contact lenses have been explored in this respect to increase bioavailability of ocular drugs, while nanoparticles have lately been utilized to increase drug bioavailability and increase drug residence duration in different tissues. The current review focuses on drug delivery and futuristic aspects of corneal protection from ocular toxicity using contact lenses.

Chronic pesticide exposure induced aberrant Notch signalling along the visual pathway in a murine model.

Pesticides aid in crop-protection against pests and increase yield. However, the xenobiotic stress exerted by pesticides leads to the deterioration of human and animal health. There is a lacuna in our knowledge about their impact on the ocular surface The present work sheds light on this gap by analysing the deterioration of visual acuity as a consequence of pesticide induced xenobiotic stress and Notch pathway dysregulation. Alteration in the expression of vital components of the notch signalling was analyzed along the visual pathway with special focus on its two terminals-the cornea and the visual cortex, by mimicking the on-field scenario regarding chronic pesticide exposure in experimental murine model (Swiss albino mice; Mus musculus). Various aspects were taken into consideration through visual acuity tests, histological evaluations, culture analyses, wound healing assays, flowcytometric evaluation, fluorescence microscopic studies etc. Complete dysregulation of key players of the Notch signalling pathway was observed in both: cells of the ocular surface as well as those in the murine visual cortex post pesticide exposure, indicating activities relating to cell proliferation, differentiation and wound healing in the pesticide exposed samples. Ultra-microscopic analyses corroborated our findings by revealing the loss of fine neural processes in the visual cortex of the pesticide exposed murine samples, thereby hinting at delayed perception to visual stimuli. In vivo evaluations of the functional capacity of the neuroanatomical structures along the visual pathway also confirmed that pesticide exposure leads to severe damage along the various parts of the visual pathway, right from the ocular surface to the visual cortex.

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.

Effect of chronic pesticide exposure on murine cornea: a histopathological, cytological and flow cytometric approach to study ocular damage by xenobiotics.

Pesticide exposure can occur directly or indirectly in an occupational setting or otherwise. The health hazards of pesticides have long been studied; however, little is known about the ocular insult of these potent chemicals. In this study, we examined the consequences of long-term pesticide exposure on the ocular tissue in animal model with special focus on the cornea. Swiss Albino mice were sacrificed to obtain the eye globes and various cytological, cytotoxic and histological evaluations, in vitro growth kinetic studies and flow cytometric analyses of select cytokeratins were performed to determine the structural and functional damage due to pesticide exposure. Our study revealed the detrimental impact of this xenobiotic insult by cataloguing the damage to each layer of the cornea wherein it was discovered that all the functional layers as well as the membranes were compromised. We hope that our investigation will pave the way for future studies in this oft overlooked area of affront caused by pesticide exposure to the ocular surface.