Dichlorvos, an organophosphate commercially available since 1961 [1] , is extensively used in agriculture, households, aircraft, and outdoor areas. Like other pesticides, it can be absorbed through the skin, ingestion, or inhalation, leading to neurotoxicity and various adverse impacts [2] . The primary mechanism of organophosphate toxicity involves acetyl cholinesterase inhibition, resulting in the accumulation of acetylcholine and subsequent symptoms of poisoning [3] . Chronic exposure to dichlorvos has been linked to health issues, including cancer and haematological disorders [4] . Dichlorvos is a widely used organophosphate insecticide that has drawn attention from all over the world because of its detrimental effects on human health and the environment. Known by another name, DDVP, this substance is used in agriculture, public health, and household pest management. Its effects on ecosystems, biodiversity, and human health are of concern [5] . Due to its poisonous qualities, there are serious dangers to human health and the environment. When ingested, inhaled, or exposed topically, there may be acute or long-term health consequences. Due to its persistence and bio accumulative nature in the environment, studies have connected dichlorvos exposure to neurological diseases, respiratory conditions, and possible carcinogenicity [6] . Furthermore, target pests have developed a resistance to pesticides as a result of the extensive agricultural use of dichlorvos, which could worsen environmental pollution [7] . International organizations have taken regulatory measures to reduce the use of dichlorvos; nevertheless, effective enforcement is still a challenge, especially in areas with weak regulatory frameworks [8] . Governments, scientists, industry stakeholders, and civil society must work together to address these issues, putting a focus on sustainable pest management techniques and the search for safer alternatives [9] . In Nigeria, dichlorvos is commonly used as a household and agricultural pesticide under various names like Nuvan, Sniper, and “Pia-pia” [10] . Despite its widespread use, there is a lack of knowledge about the haematological impacts of dichlorvos exposure in Nigerians. Blood serves as a reliable medium for assessing health status, with various parameters indicating physiological and pathological conditions in animals [11] . Cardiovascular diseases are a major global cause of death, and there is a need to understand the chronic impacts of pesticide exposure, particularly on cardiovascular health [12] . Chronic exposure to pesticides, such as organochlorines, has been associated with cardiovascular diseases through mechanisms like altered lipid metabolism [12] . Electrocardiogram (ECG) changes, including prolonged QTc interval, sinus tachycardia, and other cardiac manifestations, have been observed in acute organophosphate poisoning. Chronic pesticide exposure has been linked to non-fatal myocardial infarction and arterial peripheral disease [13] . L-arginine, an indispensable amino acid, plays a pivotal role in cardiovascular function and exhibits potential therapeutic impacts in alleviating pesticide-induced toxicity [14] . Beyond its cardiovascular contributions, L-arginine serves various essential biological functions. It contributes to acid-base balance, a clinically underappreciated aspect, as the urea cycle significantly consumes bicarbonate [15] , playing a critical role in maintaining acid-base homeostasis [15] . This amino acid significantly influences the proper functioning of the cardiovascular system (CVS). Clinical studies involving hypertensive, diabetic, and healthy individuals suggest that L-arginine can regulate vascular haemostasis [15] . Supplementation with L-arginine has been shown to ameliorate the pathology of various diseases in clinical practice [14] . Vascular endothelial dysfunctions, considered pathological changes in the cardiovascular system, often coincide with a reduction in nitric oxide (NO) synthesis [16] . The oxidative stress observed in endothelial cells is associated with vascular endothelial dysfunctions and diminished NO synthesis, factors linked to the aetiology of numerous pathological alterations in the cardiovascular system [17] . The impact of L-arginine supplementation on haematological parameters, cardiovascular response, and oxidative biomarkers in male Wistar rats exposed to dichlorvos is crucial for several reasons. First, the commonly used pesticide dichlorvos has been associated with haematotoxicity, emphasizing the need to understand and mitigate its harmful impacts. Second, the potential of the essential amino acid L-arginine to combat such toxicity remains an unstudied area. Third, this research is related to the growing concern about pesticide exposure and the need to identify protective measures to protect physiological functions. Fourth, the incorporation of arginine has the potential to provide new perspectives on toxicity mechanisms related to oxidative stress, cardiovascular, and haematological responses. It may also demonstrate protective effects via mechanisms like enhanced nitric oxide bioavailability and decreased oxidative stress [18] . This study aims to investigate the impacts of L-arginine supplementation on haematological parameters, cardiovascular biomarkers, and oxidative responses in rats exposed to dichlorvos. The research addresses a critical gap in the literature and may contribute to developing strategies to mitigate the adverse effects of pesticide exposure. The findings are expected to provide insights into the protective role of L-arginine and inform future interventions for pesticide-related health issues.

Forty (40) healthy male Wistar rats weighing between 220 - 250 g, obtained from a private breeder, were selected for the study. The use of Wistar rats in research offers a balance between practical considerations, genetic stability, and biological relevance, making them valuable models for a wide range of scientific investigations. These rats had not undergone any prior experimental interventions and were considered healthy based on the absence of stress or infection indicators. Before initiating the experiments, the rats were individually weighed after a period of acclimatization lasting two weeks. They were housed in well-ventilated plastic cages at the animal facility of the Department of Physiology, Faculty of Basic Medical Sciences, LAUTECH, Ogbomoso, Oyo State. During the research, the animals were provided with both standard diet and water under 12 hours light/12 hours dark cycle; temperature range; 25 ± 2˚C and 60% - 65% humidity. The experimental protocols adhered to the guidelines outlined in the National Research Council’s Guide for the Care and Use of Laboratory Animals.

Dichlorvos is highly toxic and can enter the body through inhalation, dermal absorption, and ingestion [31] . Inhalation is the primary exposure route in domestic use due to dichlorvos’ volatile nature. Our study found changes in haematological parameters in dichlorvos-exposed Wistar rats, indicating anaemia, contrary to previous reports [32] . The toxicants, once in the body, travel through the blood to various organs, affecting animal health. Exposure led to normocytic normochromic anaemia, possibly due to increased red blood cell destruction beyond bone marrow capacity [33] . Haematological indicators, such as platelet count, haemoglobin concentration, and erythrocyte count, were altered as a result of dichlorvos exposure. These alterations align with the haematotoxic consequences documented in the literature related to exposure to organophosphate pesticides [33] . Moreover, the observed decline in haemoglobin concentration and erythrocyte count may indicate the onset of anaemia, a known side effect of pesticide exposure [34] . However, L-arginine treatment ameliorated dichlorvos-induced anaemia, restoring blood parameters and suggesting potential immune system improvement [35] . Epidemiological evidence links pesticide exposure, including dichlorvos, to cardiovascular diseases (CVD) [13] . Dichlorvos accumulates in organs, causing toxic impacts [20] . The cardiovascular response was also significantly altered by dichlorvos exposure, as shown by changes in blood pressure, heart rate, and electrocardiographic parameters. These results are consistent with earlier research showing the cardiotoxic effects of pesticides, including organophosphates, which can cause arrhythmias and interfere with autonomic control [36] . According to [37] , sympathetic overactivity is a common reaction to stress caused by pesticides, which could explain the observed rise in heart rate and blood pressure. Blood pressure associations with pesticides vary, with some studies reporting positive links [38] , while others show negative associations [39] . Dichlorvos exposure increased blood pressure in rats, but L-arginine treatment alleviated this impact. This strongly agrees with a previous study [17] . The cardiovascular system’s homeostasis of vascular tone, interactions between the vascular wall and circulating blood cells (primarily leukocytes and thrombocytes), and vascular structure all depend critically on the NO produced by eNOS in response to stimulation of mechanoreceptors by the flowing blood’s shear stress. These functions have been thoroughly addressed in recent years [40] . One of the main pathogenic factors in the development of vascular disorders such as atherosclerosis, hypertension, and diabetic angiopathy is impaired NO formation or function in the vasculature [40] . Conversely, it has been demonstrated that a primary factor contributing to the loss of vascular resistance in septic shock is the overproduction of NO by iNOS [41] . Consequently, L-arginine-dependent metabolic pathways are important determinants of a number of pathological diseases, and L-arginine plasma content is strictly regulated. DVPP-exposed rats displayed elevated heart rate and ECG abnormalities, consistent with the cholinergic impacts of dichlorvos [13] . L-arginine treatment reduced heart rate and mitigated ECG changes, suggesting its cardio-protective potential. Histopathological examination revealed dichlorvos-induced heart damage, which L-arginine partially alleviated. Biomarkers such as CK-MB, LDH, and Troponin I indicated cardiac injury, with L-arginine reducing their levels. L-arginine, a semi-essential amino acid, plays roles in protein synthesis, immune function, and vasodilation through nitric oxide production [42] . Supplementation decreases cardiac injury markers and could potentially enhance antioxidant defense [43] . Our research showed that after being exposed to dichlorvos, there was a significant rise in oxidative stress indicators, such as malondialdehyde (MDA) levels, and a decrease in antioxidant enzyme activity. According to [34] , these results point to increased lipid peroxidation and compromised antioxidant defense mechanisms, both of which are signs of oxidative stress. According to [44] , oxidative stress is a critical factor in the pathophysiology of pesticide-induced toxicity, as it leads to tissue damage and malfunction. It’s interesting to note that in the parameters under investigation, L-arginine supplementation had protective benefits against dichlorvos-induced toxicity. Strong antioxidant and vasodilatory qualities of L-arginine, a precursor of nitric oxide (NO), may mitigate the oxidative stress and vascular dysfunction brought on by pesticide exposure [43] . Furthermore, it has been demonstrated that supplementing with L-arginine increases NO bioavailability, which enhances endothelial function and improves cardiovascular health [45] . Supplementation with L-arginine may lessen the negative effects of dichlorvos on haematological markers and cardiovascular response by reducing oxidative stress and maintaining cardiovascular homeostasis. L-arginine, as well as the expression and activity of the cationic amino acid transporters (CAT), which are in charge of bringing L-arginine into the cell, are prerequisites for appropriate endogenous iNOS activity during inflammation [46] . Serum arginine levels in healthy humans vary from 60 to 100 μmol [47] and comparable values for rats are reported [48] . Depletion of available substrate, restricted availability, or disruption of CAT activity can result in reduced endothelium iNOS-derived NO production and reduced resistance to atherosclerosis.

In summary, this investigation explored the impact of L-arginine supplementation on male Wistar rats exposed to dichlorvos. The findings indicated significant alterations in blood parameters, cardiac metrics, and oxidative stress responses due to dichlorvos exposure. Notably, L-arginine treatment demonstrated efficacy in ameliorating anaemia and cardiac issues induced by dichlorvos, suggesting its potential therapeutic utility. Additionally, the study highlighted that L-arginine supplementation influenced antioxidant enzyme levels, mitigating pesticide-induced damage in rats. The results suggest that L-arginine may offer a beneficial intervention to alleviate the adverse impacts of dichlorvos on blood and heart health, paving the way for potential treatments for pesticide poisoning.

Findings on L-arginine’s protective role against dichlorvos-induced haemotoxicity have broad implications for pesticide-related health issues, especially in agricultural workers and those exposed environmentally. Pesticides globally pose significant public health risks, including haematological, cardiovascular, and neurological disorders. Understanding pesticide toxicity mechanisms and interventions is vital. L-arginine supplementation could protect against haematotoxicity and cardiovascular issues in dichlorvos exposure. This offers therapeutic and preventive potential, especially for acute poisoning or chronic exposure situations. Clinical studies on L-arginine’s efficacy in pesticide-exposed populations may reveal insights into its antioxidant and cardiovascular benefits. Preventive measures, including safety protocols and consuming L-arginine-rich foods, are crucial in reducing pesticide risks. Advocating for safer pesticide practices and educating the public, including agricultural workers, is essential. Collaborative efforts among medical professionals, scientists, policymakers, and agricultural stakeholders are necessary to develop comprehensive strategies addressing pesticide-related health issues. This study demonstrates L-arginine’s efficacy in mitigating dichlorvos-induced cardiac and blood parameter changes, suggesting its therapeutic potential. L-arginine supplementation also modulates antioxidant enzyme levels, mitigating pesticide-induced harm. These findings underscore L-arginine’s promise in treating pesticide poisoning, advancing potential interventions for pesticide-exposed individuals.

Saka, W.A., Igbayilola, Y.D., Lawan, H.J., Muftaudeen, T.K., Adejumo, R., Alu, T.D., Ikuomola, M., Ojelere, J.T. and Adegoke, V.O.: Designed and conceived the investigations; carried out the investigation; analyzed and interpreted the data; contributed kits, equipment, tools for data analysis and wrote the manuscript.