An extensive review of arsenic dynamics and its distribution in soil-aqueous-rice plant systems in south and Southeast Asia with bibliographic and meta-data analysis.

Millions of people worldwide are affected by arsenic (As) contamination, particularly in South and Southeast Asian countries, where large-scale dependence on the usage of As-contaminated groundwater in drinking and irrigation is a familiar practice. Rice (Oryza sativa) cultivation is commonly done in South and Southeast Asian countries as a preferable crop which takes up more As than any other cereals. The present article has performed a scientific meta-data analysis and extensive bibliometric analysis to demonstrate the research trend in global rice As contamination scenario in the timeframe of 1980-2023. This study identified that China contributes most with the maximum number of publications followed by India, USA, UK and Bangladesh. The two words 'arsenic' and 'rice' have been identified as the most dominant keywords used by the authors, found through co-occurrence cluster analysis with author keyword association study. The comprehensive perceptive attained about the factors affecting As load in plant tissue and the nature of the micro-environment augment the contamination of rice cultivars in the region. This extensive review analyses soil parameters through meta-data regression assessment that influence and control As dynamics in soil with its further loading into rice grains and presents that As content and OM are inversely related and slightly correlated to the pH increment of the soil. Additionally, irrigation and water management practices have been found as a potential modulator of soil As concentration and bioavailability, presented through a linear fit with 95% confidence interval method.

Co-administration of L-Ascorbic Acid and α-Tocopherol Alleviates Arsenic-Induced Immunotoxicities in the Thymus and Spleen by Dwindling Oxidative Stress-Induced Inflammation.

Herein, we investigated whether L-ascorbic acid (L-AA) and α-tocopherol (α-T) co-administration has the potential to alleviate arsenic-induced immunotoxicities in the thymus, spleen, and circulating leukocytes. Forty-eight adult male Wistar rats were randomly divided into four groups before the treatment: group I (control); group II (sodium arsenite, 3 mg/kg/day/rat); group III (sodium arsenite + L-AA (200 mg/kg/day/rat) and α-T (400 mg/kg/day/rat)); group IV (L-AA and α-T). The result showed that sodium arsenite exposure (consecutive 30 days) caused weight reduction, structural alterations in the thymus and spleen, accompanied by a decrease in thymocyte and splenocyte count. Decreased superoxide dismutase and catalase activity, increased malondialdehyde and protein-carbonyl content, reduced Nrf2 and Bcl2 expression, and increased p-ERK, NF-kß, Bax, and cleaved-caspase-3 expression were also observed in the thymus and spleen of arsenic-exposed rats. Enhanced plasma ACTH and corticosterone, ROS-induced apoptosis of lymphocytes were also observed. L-AA and α-T co-administration has the potential to abrogate the deleterious impact of arsenic on the thymus, spleen, and circulating lymphocytes. Whole transcriptome analysis of leukocytes revealed that arsenic treatment augmented the expression of Itga4, Itgam, and MMP9 genes, which might help in transient migration of the leukocytes through the endothelial cell layer. Co-administration with L-AA and α-T maintained Itga4, Itgam, and MMP9 gene expression within leukocytes at a lower level.

Ascorbic acid modulates immune responses through Jumonji-C domain containing histone demethylases and Ten eleven translocation (TET) methylcytosine dioxygenase.

Ascorbic acid is a redox regulator in many physiological processes. Besides its antioxidant activity, many intriguing functions of ascorbic acid in the expression of immunoregulatory genes have been suggested. Ascorbic acid acts as a co-factor for the Fe+2 -containing α-ketoglutarate-dependent Jumonji-C domain-containing histone demethylases (JHDM) and Ten eleven translocation (TET) methylcytosine dioxygenasemediated epigenetic modulation. By influencing JHDM and TET, ascorbic acid facilitates the differentiation of double negative (CD4- CD8- ) T cells to double positive (CD4+ CD8+ ) T cells and of T-helper cells to different effector subsets. Ascorbic acid modulates plasma cell differentiation and promotes early differentiation of hematopoietic stem cells (HSCs) to NK cells. These findings indicate that ascorbic acid plays a significant role in regulating both innate and adaptive immune cells, opening up new research areas in Immunonutrition. Being a water-soluble vitamin and a safe micro-nutrient, ascorbic acid can be used as an adjunct therapy for many disorders of the immune system.

Casein and pea enriched high-protein diet attenuates arsenic provoked apoptosis in testicles of adult rats.

Arsenic toxicity is a major health issue that also threats male reproductive system leading to impairment of fertility. The antioxidant capacity of casein and pea enriched formulated high-protein diet (FHPD) is found to be effective in different toxicity management. The present study was endeavored to investigate the mitigatory aspect of FHPD on arsenic stimulated testicular apoptosis. Adult male rats were maintained on either normal diet as control (Gr I, n = 8) and arsenic (As2O3) treated at a dose of 3 mg/kg/rat/day (Gr II, n = 8) or on isocaloric FHPD as supplemented (Gr III, n = 8) with same dose of arsenic for 30 consecutive days. Testicular histomorphometry, spermatokinetics, testicular functional marker enzymes, serum gonadotrophins, oxidative stress markers, testicular deoxyribonucleic acid (DNA) damage, and apoptosis markers were evaluated to assess the reprotoxicity of arsenic and subsequent protection by FHPD. FHPD protected the histopathological alterations and also restored normal spermatogenesis. Altered enzymatic activities of testicular functional markers like lactate dehydrogenase, γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase were also regularized. FHPD also reinstated the normal level of follicle stimulating hormone (FSH), luteinising hormone (LH), and also normalized the enzymatic activities of testicular glutathione peroxidase and glutathione reductase. Testicular DNA damage was also prevented by FHPD supplementation. Testicular apoptosis marked by the altered messenger ribonucleic acid and protein expression of apoptotic markers like Bax, Bcl-2, caspase 9, and caspase 3 were also attenuated upon FHPD supplementation along with diminution of arsenic accumulation in testicular tissues. FHPD not only mitigated the adverse effects of arsenic induced gonadotoxicity but also helped in sustaining the normal reproductive functions.

Molecular basis of fluoride toxicities: Beyond benefits and implications in human disorders.

Detrimental impacts of fluoride have become a global concern for several decades. Despite its beneficial role which is restricted only in skeletal tissues, deleterious effects are also observed in soft tissues and systems. The generation of enhanced oxidative stress is the commencement of excess fluoride exposure which may lead to cell death. Fluoride causes cell death through autophagy via Beclin 1 and mTOR signaling pathways. Beside these, several organ specific anomalies through different signaling pathways have been documented. Mitochondrial dysfunction, DNA damage, autophagy and apoptosis are the damaging outcomes in case of hepatic disorders. Urinary concentration defects and cell cycle arrest have been reported in renal tissues. Abnormal immune response has been characterized in the cardiac system. Cognitive dysfunction, neurodegenerative condition and learning impairment have also been observed. Altered steroidogenesis, gametogenic abnormalities, epigenetic alterations and birth defect are the major reprotoxic conclusions. Abnormal immune responses, altered immunogenic proliferation, differentiation as well as altered ratio of immune cells are well-defined anomalies in the immune system. Though the mechanistic approach of fluoride toxicity in physiological systems is common, it follows different signaling cascades. This review emphasizes diverse signaling pathways which are the targets of overexposed fluoride.

Attenuation of sodium arsenite mediated ovarian DNA damage, follicular atresia, and oxidative injury by combined application of vitamin E and C in post pubertal Wistar rats.

Arsenic being a toxic metalloid ubiquitously persists in environment and causes several health complications including female reproductive anomalies. Epidemiological studies documented birth anomalies due to arsenic exposure. Augmented reactive oxygen species (ROS) generation and quenched antioxidant pool are foremost consequences of arsenic threat. On the contrary, Vitamin E (VE) and C (VC) are persuasive antioxidants and conventionally used in toxicity management. Present study was designed to explore the extent of efficacy of combined VE and VC (VEC) against Sodium arsenite (NaAsO2) mediated ovarian damage. Thirty-six female Wistar rats were randomly divided into three groups (Grs) and treated for consecutive 30 days; Gr I (control) was vehicle fed, Gr II (treated) was gavaged with NaAsO2 (3 mg/kg/day), Gr III (supplement) was provided with VE (400 mg/kg/day) & VC (200 mg/kg/day) along with NaAsO2. Marked histological alterations were evidenced by disorganization in oocyte, granulosa cells and zona pellucida layers in treated group. Considerable reduction of different growing follicles along with increased atretic follicles was noted in treated group. Altered activities ofΔ5 3ß-Hydroxysteroid dehydrogenase and 17ß-Hydroxysteroid dehydrogenase accompanied by reduced luteinizing hormone, follicle-stimulating hormone and estradiol levels were observed in treated animals. Irregular estrous cyclicity pattern was also observed due to NaAsO2 threat. Surplus ROS production affected ovarian antioxidant strata as evidenced by altered oxidative stress markers. Provoked oxidative strain further affects DNA status of ovary. However, supplementation with VEC caused notable restoration from such disparaging effects of NaAsO2 toxicities. Antioxidant and antiapoptotic attributes of those vitamins might be liable for such restoration.

Impact of hyperglycemia on the expression of GLUT1 during oral carcinogenesis in rats.

BACKGROUND: On the background of the epidemiological link between diabetes and oral cancer, the present study aimed to analyze the potential involvement of selected glucose transporters (GLUT1/GLUT3/GLUT4), if any, in such putative association. METHODS AND RESULTS: Oral carcinogenesis was induced by 4-nitroquinoline N-oxide in 10 non-diabetic and 10 diabetic rats; 8 non-diabetic and 7 diabetic rats served as controls. Expressions of selected GLUTs at mRNA and protein levels were analyzed in oral tissue (normal/lesion) by quantitative real-time PCR and immunohistochemistry respectively. Premalignant lesions (hyperplasia/dysplasia/carcinoma-in-situ) appeared on tongues of carcinogen-treated animals. Significant increase of GLUT1mRNA level was seen from normal to lesion tongues, along increasing lesion grades (from hyperplasia/mild dysplasia to moderate/severe dysplasia) and in lesions induced under hyperglycemic condition than that induced under normoglycemic one; a similar trend was found in transcript variant-1 of GLUT1, but not in variant-2. GLUT3 and GLUT4 mRNA levels were comparable among lesions irrespective of grades and glycemic status. Concordant to mRNA level, overall expression of GLUT1 protein was higher in tongue lesions in presence of hyperglycemia than in absence of such condition; non-lesion portions of tongues exposed to carcinogen showed a similar trend. Moreover in carcinogen-treated groups, non-lesion and lesion portions of tongues under hyperglycemic condition showed predominantly membranous expression for GLUT1 which was again significantly higher than equivalent portions of tongue under normoglycemic condition. CONCLUSION: Hyperglycemia seemed to favor GLUT1 over-expression and membrane localization of the protein during oral carcinogenesis. GLUT1 transcript variant-1 appeared to be more important than variant-2 in disease pathogenesis.

Vitamin C and E supplementation can ameliorate NaF mediated testicular and spermatozoal DNA damages in adult Wistar rats.

OBJECTIVE: Present study was designed to explore the efficacy of vitamin C and E (VC&VE) against fluoride mediated testicular, epididymal and spermatozoal anomalies. MATERIALS AND METHODS: Thirty two adult Wistar rats were divided into four groups. Group-I was control; Group-II received sodium fluoride (NaF) at 15 mg/kg/day dose; Group-III was provided with VC (200 mg/kg/day) and VE (400 mg/kg/day) plus NaF; Group-IV received only VC&VE. Structural integrity and oxidative stress markers (superoxide dismutase, catalase, malondialdehyde and protein carbonyl) of testis and epididymis were assessed. Spermatozoal parameters (count, motility, viability and hypo-osmotic swelling) were evaluated. Testicular functional maker enzymes (acid phosphatase, alkaline phosphatase and lactate dehydrogenase) were also assessed. Integrity of testicular and spermatozoal DNA was evaluated. Testicular fluoride content was measured. RESULT: Fluoride induced structural changes and alterations of oxidative stress markers were observed in testis and epididymis. Spermatozoal potentials were altered and reduced activities of testicular functional marker enzymes were observed. Fluoride caused testicular and spermatozoal DNA damages. VC&VE supplementation resulted in protection from all fluoride mediated alterations and helped in attenuating testicular fluoride accumulation. CONCLUSION: Antioxidant properties of VC&VE ameliorated fluoride mediated reproductive damages but only supplementation did not exhibit any notable effect compared to control rats.

Molecular perspective concerning fluoride and arsenic mediated disorders on epididymal maturation of spermatozoa: A concise review.

Epididymis is a complex tubular structure of male reproductive system where spermatozoa undergo maturation and gain the fertilizing ability. Epididymal pseudostratified columnar epithelium with different cell types play imperative role by their secretory properties and enrich the luminal microenvironment necessary for achieving spermatozoal motility. During epididymal transit several secretory proteins like P26h, SPAG11, HSPD1 and many others are deposited on spermatozoal surface. At the same time spermatozoal proteins are also modified in this intraluminal milieu, which include cyritestin, fertilin, CE9 and others. Natural and anthropogenic activities disclose various environmental pollutants which affect different physiological systems of animals and human being. Likewise, reproductive system is also being affected. Fluoride causes structural alterations of caput and cauda segments of epididymis. Redox homeostasis and functional integrity are also altered due to diminished activities of SOD1, GR, Crisp2, Lrp2 and other important proteins. On the contrary arsenic affects mostly on cauda segment. Redox imbalance and functional amendment in epididymis have been observed with arsenic revelation as evidenced by altered genomic appearance of SOD, GST, catalase, Ddx3Y, VEGF and VEGFR2. This review is dealt with structure-function interplay in normal epididymal spermatozoal maturation along with subsequent complications developed under fluoride and arsenic toxicities.

Fluoride induced testicular toxicities in adult Wistar rats.

Fluoride is essential for the development of teeth and bone but its excessive exposure causes reprotoxic effects. We have studied the graded effects of different doses of sodium fluoride (NaF) on 24 adult Wistar rats which were randomly divided into four groups (n = 6). All the rats were given normal diet prepared in our laboratory. Control (group I) rats were received vehicle only and treated rats (group II, III, and IV) were administered NaF orally at 10, 15, and 20 mg/kg/d doses, respectively, for 30 consecutive days. Gravimetric index of testis was decreased significantly in group III and IV rats but such changes were not observed in the accessory reproductive organs. Marked alterations in number, motility, viability, and plasma membrane functional integrity of caudal spermatozoa were noted in most of the treated groups. Noticeable alterations in testicular histoarchitecture were observed in group III and IV rats. Graded Changes of testicular redox homeostasis were noted by assessment of enzymatic (superoxide dismutase [SOD], catalase, glutathione s-transferase [GST], and glutathione peroxidase [GPx]) and nonenzymatic (malondialdehyde [MDA] and protein carbonyl [PC]) markers. Changes of testicular functional markers (acid phosphatase [ACP], alkaline phosphatase [ALP], and lactate dehydrogenase (LDH) activity) were noted in group III and IV rats. DNA fragmentation assay proved the possibility of DNA damage caused by oxidative stress, as evidenced by prominent trailing pattern of fragmented testicular genomic DNA from group III and IV rats. The study concludes that fluoride-mediated oxidative stress not only impedes the structural and functional facets of testis but also results in testicular DNA damage.

High-Protein Diet Ameliorates Arsenic-Induced Oxidative Stress and Antagonizes Uterine Apoptosis in Rats.

Arsenic toxicity purportedly threats a broad spectrum of female reproductive functions. We investigated the remedial role of a casein- and pea protein-enriched high-protein diet (HPD) in combating the arsenic insult. Cyclic female rats maintained on standard diet (n = 6) or an isocaloric HPD (n = 6) were gavaged with As2O3 at 3 mg/kg BW/rat/day (n = 12) for 28 days. Vehicle-fed rats (n = 6) maintained on the standard diet served as the control. We monitored the estrus cycles and performed the histomorphometric analyses of the uterus and ovary. Uterine luminal epithelial (ULE) ultrastructure was appraised by scanning electron microscopy. Uterine oxidative stress was evaluated in the forms of ROS generation and activities of the ROS scavengers. The uterine apoptotic manifestation was blueprinted by Western blot analysis of caspase-3 and Bax expression. Arsenic treatment arrested the follicular maturation and disrupted the estrus cycles with a typical increase in the diestrus index. Shrunken endometrial glands and thinned microvilli density of the ULE reflected loss of cell polarity and mislaid uterine homeostasis. Increased ROS generation and attenuated activities of the ROS scavengers marked a state of uterine oxidative imbalance and loss of redox regulation. Superfluous expression of procaspase-3, cleaved caspase-3, and Bax mirrored an inflated state of uterine apoptosis. HPD supplementation, by and large, counteracted these arsenic impacts and maintained the frameworks close to the control levels. In conclusion, arsenic mediates its reproductive toxicity, at least in part, by upsetting the uterine ROS homeostasis and redox regulation. Pea proteins and casein-supplemented HPD can counteract the arsenic effects and maintain the reproductive functions.

The effect of coadministration of α-tocopherol and ascorbic acid on arsenic trioxide-induced testicular toxicity in adult rats.

BACKGROUND: Arsenic, acting as an endocrine disruptor, causes reproductive malfunctions. Studies have been undertaken to find out whether the co-supplementation of α-tocopherol and ascorbic acid (AT-AA) could reduce the arsenic-induced testicular toxicity caused by oxidative stress and resulting DNA damage. METHODS: Adult male Wistar rats (120±10 g) were given arsenic trioxide [3 mg/kg body weight (b.wt.) per day] for 30 consecutive days and the supplement group received α-tocopherol (400 mg/kg b.wt. per day) and ascorbic acid (200 mg/kg b.wt. per day). Reproductive functions were evaluated with respect to the histoarchitecture, gametokinetic activity, androgenic potential, glutathione-dependent antioxidant status and DNA damage of the testis. RESULTS: Arsenic treatment caused marked reduction in the relative weight of the testis (p<0.05) but showed no effect on body weight. The number of germ cells at stage VII of the spermatogenic cycle (p<0.01), the seminiferous tubular diameter (p<0.001) and Leydig cell nuclear area (p<0.01) were significantly reduced. Notable decrease in the activities of testicular Δ5, 3ß-HSD (p<0.05) and 17ß-HSD (p<0.01) with a concomitant fall in serum testosterone level (p<0.01) along with significant diminution in testicular glutathione S-transferase (p<0.05) activity and reduced glutathione level (p<0.01) were observed. Significant DNA damage (p<0.001) in spermatogenic cells was also noted. All these alterations including DNA strand breakage were seen to be protected with the coadministration of AT-AA. CONCLUSIONS: The data suggest that the protection of testicular toxicity in arsenic-exposed adult rats is possible with combined coadministration of AT-AA.