Tamarind seed coat ameliorates fluoride induced cytotoxicity, oxidative stress, mitochondrial dysfunction and apoptosis in A549 cells.

Fluoride (F) is well-known for its prophylactic use over several decades to prevent dental caries via topical application or supplementation through drinking water [1]. F and their compounds are used in a variety of industries, for example, in the production of aluminium, steel, phosphate fertilizers, phosphoric acid, glass, ceramic, and brick products. They appear as pollutants emitted in the air in the working environment and outside the workplace [2]. The occupational and environmental exposure to F compounds causes deleterious effects on hard and soft tissues, including the lungs [3]. In industrial exposures to gaseous and particulate F, their absorption is mainly through the respiratory tract [4]. Pneumoconiosis has been reported in men working with fluor-spar deposits [5]. Epidemiological studies have also found that F dusts and gases (at levels as low as 0.05 mg/mg³) are the key irritants responsible for the higher rate of respiratory illness such as work related asthmatic symptoms, chronic bronchitis, and abnormal lung function in workers from aluminium pot room, welding and small-scale enamel enterprises [6], [7]. Pulmonary and nasal irritations with edema were also reported following repeated exposures to F [8]. Pollutants from the aluminium industry may also influence the respiratory health of the general population. A significant association between air pollution and bronchial hyper responsiveness in children living within the vicinity of an aluminium plant [9]. The involvement of the rib cage skeletal fluorosis causing restrictive lung disease, shortness of breath and reduction of vital capacity in patients living in endemic fluorotic areas was reported in India [10]. Further, F aerosols released from the household activities such as coal burning resulted in the increased incidence of respiratory symptoms in adults [11].

Hyperaemia, apoptosis and necrosis of epithelial cells, marked destructions of lung tissue were also reported in experimental fluorosis [12], [13]. In addition, sodium fluoride (NaF) exposure during gestation has resulted in histopathological changes like alveolar cell hyperplasia and necrosis in the lungs of rats over several generations [14]. Occurrence of apoptosis was reported in epithelial lung cells on expsoure to F [15]. In this study, we hypothesized that F may induce apoptotic cell death via [Ca²⁺]_i overload, oxidative stress and mitochondrial dysfunction in lung epithelial cells, A549.

The potential role of oxidative stress and the cell injury associated with F poisoning suggests that phytochemicals found in fruits, and vegetables may be effective against reactive oxygen species (ROS) mediated injury [16], [17]. Tamarind (Tamarindus indica) is one of the traditional medicinal plants in tropical countries, including India and their fruits, leaves and seeds were reported to have antidiabetic, hypoglycemic and antioxidant activities [18]. Further, tamarind fruit pulp [18], [19] has been reported to have a protective effect against experimental fluorosis. The seeds [20] and fruit shells [21] have been shown as adsorbents in defluoridation process. However, the effect of seeds on in vitro systems is yet to be studied. In addition, the tamarind seed and seed coat (by-product of tamarind gum preparation), rich in polysaccharides and oligomeric procyanidins have been reported to possess antioxidant properties [22]. In view of all the above, the present study was aimed to investigate whether tamarind seed coat extract (TSCE) alleviates F toxicity by reducing F content and maintaining [Ca²⁺]_i status and to elucidate the underlying molecular mechanisms in human lung epithelial cells, A549.