The therapeutic potential of isosakuranetin against perfluorooctane sulfonate instigated cardiac toxicity via modulating Nrf-2/Keap-1 pathway, inflammatory, apoptotic, and histological profile.

Perfluorooctane sulfonate (PFOS) is a pervasive organic toxicant that damages body organs, including heart. Isosakuranetin (ISN) is a plant-based flavonoid that exhibits a broad range of pharmacological potentials. The current investigation was conducted to evaluate the potential role of ISN to counteract PFOS-induced cardiac damage in rats. Twenty-four albino rats (Rattus norvegicus) were distributed into four groups, including control, PFOS (10 mg/kg) intoxicated, PFOS + ISN (10 mg/kg + 20 mg/kg) treated, and ISN (20 mg/kg) alone supplemented group. It was revealed that PFOS intoxication reduced the expressions of Nrf-2 and its antioxidant genes while escalating the expression of Keap-1. Furthermore, PFOS exposure reduced the activities of glutathione reductase (GSR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), Heme oxygenase-1 (HO-1) and glutathione (GSH) contents while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, PFOS administration upregulated the levels of creatine kinase-MB (CK-MB), troponin I, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Moreover, the levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were increased after PFOS intoxication. Additionally, PFOS exposure downregulated the expression of Bcl-2 while upregulating the expressions of Bax and Caspase-3. Furthermore, PFOS administration disrupted the normal architecture of cardiac tissues. Nonetheless, ISN treatment remarkably protected the cardiac tissues via regulating aforementioned dysregulations owing to its antioxidative, anti-inflammatory, and antiapoptotic properties.

Curative effects of tectochrysin on paraquat-instigated testicular toxicity in rats: A biochemical and histopathological based study.

Background: Paraquat (PQ) is a herbicide that is used globally in the agriculture sector to eradicate unwanted weeds, however it also induces significant damages in various organs of the body such as testes. Tectochrysin (TEC) is an important flavonoid that shows versatile therapeutic potentials. Currently, there is no established antidote to cure PQ-induced testicular toxicity. Objective: The present study was conducted to evaluate the ameliorative effects of TEC against PQ prompted testicular damage. Methods: Sprague-Dawley rats (n = 48) were used to conduct the trial. Rats were allocated in to 4 groups i.e., Control, PQ administrated group (5 mgkg-1), PQ + TEC co-administrated group (5 mgkg-1 + 2.5 mgkg-1) and TEC only administrated group (2.5 mgkg-1). The trial was conducted for 8 weeks. The activity of anti-oxidants and the levels of MDA and ROS were determined by spectrophotometric method. Steroidogenic enzymes as well as apoptotic markers expressions were evaluated by qRT-PCR. The level of hormones and inflammatory indices was quantified by enzyme-linked immunosorbent assay. Results: PQ exposure markedly (P < 0.05) disturbed the biochemical, spermatogenic and histological profile in the rats. Nevertheless, TEC treatment considerably (P < 0.05) increased CAT, GPx GSR and SOD activity, besides decreasing MDA and ROS contents. TEC administration also increased sperm viability, count and motility. 17ß-HSD, 3ß-HSD, StAR and Bcl-2 expressions were also increased following TEC administration. The supplementation of TEC substantially (P < 0.05) decreased Bax, Caspase-3 expression and the levels of inflammatory markers i.e., interleukin-1ß (IL-1ß), interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) activity. Additionally, the levels of plasma testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were increased following TEC supplementation. Furthermore, TEC supplementation considerably decreased sperm structural abnormalities and histomorphological damages of the testes. The mitigative role of TEC might be due to its anti-inflammatory, anti-apoptotic, androgenic and anti-oxidant potentials. Conclusion: Taken together, it is concluded that TEC can be used as a potential candidate to treat testicular toxicity.

Evaluation of possible attenuative role of chrysoeriol against polyethylene microplastics instigated testicular damage: A biochemical, spermatogenic and histological study.

The current study was designed to evaluate the protective role of chrysoeriol against polyethylene microplastics (PE-MP) induced testicular damage. Forty eight male rats were distributed into 4 equal groups: vehicle control, PE-MP administrated, PE-MP + chrysoeriol co-administrated and only chrysoeriol supplemented group. The administration of PE-MP significantly reduced the activities of anti-oxidant enzymes, i.e., glutathione peroxidase, catalase, glutathione reductase and superoxide dismutase, whereas the levels of reactive oxygen species and malondialdehyde were increased. PE-MP exposure increased the levels of inflammatory markers (TNF-α, 1L-1ß, NF-κß, IL-6 & COX-2). Additionally, a considerable increase was observed in dead sperms number, abnormality of sperms (tail, midpiece and head), while a potential decrease was noticed in sperm motility in PE-MP treated rats. The expressions of steroidogenic enzymes were also decreased in PE-MP administrated group. The levels of plasma testosterone, luteinizing & follicle stimulating hormone were decreased in PE-MP treated group. Moreover, Bax and Caspase-3 expressions were increased, whereas Bcl-2 expressions were reduced. Furthermore, histopathological analysis showed that PE-MP exposure considerably damaged the testicular tissues. However, chrysoeriol supplementation potentially decreased all the adverse effects induced by PE-MP. Taken together, our findings indicate that chrysoeriol holds significant potential to avert PE-MP-induced testicular damage due to its androgenic, anti-apoptotic, anti-oxidant and anti-inflammatory nature.

Biochemical, Genotoxic and Histological Implications of Polypropylene Microplastics on Freshwater Fish Oreochromis mossambicus: An Aquatic Eco-Toxicological Assessment.

In recent years, polypropylene microplastic has persisted in freshwater ecosystems and biota, forming ever-growing threats. This research aimed to prepare polypropylene microplastics and evaluate their toxicity to the filter feeder Oreochromis mossambicus. In this research, fish were given a dietary supplement of polypropylene microplastics at 100, 500, and 1000 mg/kg for acute (96 h) and sub-acute (14 days) durations to assess toxic effects on liver tissues. FTIR results revealed the presence of polypropylene microplastic in their digestion matter. The ingestion of microplastics in O. mossambicus led to fluctuations in homeostasis, an upsurge in reactive oxygen species (ROS) levels, an alteration in antioxidant parameters, including superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and glutathione peroxidase (GPx); a promotion in the oxidation of lipid molecules; and a denaturation in the neurotransmitter enzyme acetylcholinesterase (AChE). Our data indicated that sustained exposure to microplastics (14 days) produced a more severe threat than acute exposure (96 h). In addition, higher apoptosis, DNA damage (genotoxicity), and histological changes were found in the liver tissues of the sub-acute (14 days) microplastics-treated groups. This research indicated that the constant ingestion of polypropylene microplastics is detrimental to freshwater environments and leads to ecological threats.

Evaluation of the Possible Protective Role of Nobiletin against Arsenic-Induced Liver Damage in Male Albino Rats.

Arsenic (As) is a toxic contaminant present in organic and inorganic forms in the environment. Nobiletin (NOB) is a polymethoxy flavone that has recently gained substantial consideration due to its curative impacts. The present experiment was conducted to assess the hepatoprotective efficiency of NOB on As-generated hepatotoxicity. Twenty-four adult rats were equally distributed into four groups and designated as control, As (50 mg/kg)-treated, As + NOB (50 mg/kg and 25 mg/kg, respectively), and NOB (25 mg/kg)-treated groups. After 30 days, experimental animals were decapitated, then blood and tissue samples were collected for further analysis. The group treated with As showed a significant decrease in the activity of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione (GSH), glutathione reductase (GSR), and total antioxidant status (TAS), and a substantial increase in the accumulation of As in liver tissues, levels of total oxidant status (TOS), hydrogen peroxide (H2O2), and lipid peroxidation (TBARS). Significant increases in alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) levels were observed in As-treated rats. Moreover, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, interleukin (IL)-6, and cyclo-oxygenase (COX)-2 activity, as well as the levels of pro-apoptotic markers (Bax, Caspase-3, and Caspase-9) were increased on exposure to As. In contrast, the anti-apoptotic marker (Bcl-2) level was significantly decreased. As administration showed a significant disturbance in hepatic tissue histology. However, cotreatment of NOB with As considerably increased the antioxidant enzyme activity, with a noteworthy reduction in the deposition of As in hepatic tissues, TBARS, and H2O2 levels. NOB-administrated rats showed considerable recovery in terms of inflammation, apoptosis, and histological damage. Hence, NOB can be considered a useful curative compound due to its medicinal properties against As-prompted hepatotoxicity.

Fishing Cat Scats as a Biomonitoring Tool for Toxic Heavy Metal Contamination in Aquatic Ecosystems.

Mangrove forest is one of the productive ecosystems that provide essential habitats for various fauna as breeding and feeding drives. However, heavy metal pollution in the mangrove forest has led to severe health problems for several aquatic species. Biomonitoring of metals using a nondestructive method is an emerging technique. Scats of the fishing cat (Prionailurus viverrinus) were collected from five locations in the Godavari estuary mangrove habitats, Coringa Wildlife Sanctuary, Andhra Pradesh, India, to determine the level of various metals. An opportunistic method was applied to collect scats in the mangrove forest. Six scat samples were collected from each of the sampling sites. The following prey species, such as crabs, fishes, birds, rodents, plants, plastics, and unidentifiable prey matters, were found in the scats. Select metals, such as chromium (Cr), copper (Cu), and lead (Pb) were analyzed from the scats of the fishing cat since they intensively influence the physiology and behavior of top predators. The concentration of Cu in fishing cat scats was higher than the other two metals assessed. Metals showed statistically substantial variation across locations (p < 0.05). According to the current study, heavy metals may significantly threaten the fishing cat in the Coringa Wildlife Sanctuary. The fishing cat is a vulnerable species in accordance with the ICUN categories. Due to pollution and other human pressures, the fishing cat may soon be categorized as a threatened or endangered species; the research advises that authorities should prioritize the protection of the vulnerable species of the fishing cat from the Coringa Wildlife Sanctuary, Andhra Pradesh, India.

Ingestion and impacts of water-borne polypropylene microplastics on Daphnia similis.

Polypropylene microplastics are the leading contaminant in aquatic environments, although research on their toxicity remains scarce. The proposed research focuses on the harmful consequences of acute exposure to polypropylene microplastics in Daphnia similis. This work converts widely available polypropylene bags into microplastics using xylene. FTIR findings demonstrated the lack of xylene residue in the produced polypropylene microplastic particles, which were spherical and ranged in size from 11.86 to 44.62 µm (FE-SEM). The results indicate that acute exposure to polypropylene microplastics causes immobility in D. similis. Ingestion of microplastics enhances the generation of reactive oxygen species (ROS), as shown by biochemical studies. Due to the production of free radicals in D. similis, the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) and a non-antioxidant enzyme of reduced glutathione (GSH) and also oxidative stress effects in lipid (lipid peroxidation - LPO), protein (carbonyl protein - CP) were increased. Additionally, the amount of the neurotransmitter enzyme acetylcholinesterase (AChE) activity was decreased. These findings indicate that the accumulation of polypropylene microplastics in the bodies of filter-feeding organisms should aggravate toxicity in the freshwater environment.

Detecting Aquatic Pollution Using Histological Investigations of the Gills, Liver, Kidney, and Muscles of Oreochromis niloticus.

The present study aimed to determine the degree of changes in the histological architecture of the liver, gills, kidneys, and muscles of fish Oreochromis niloticus collected from different polluted river sites. Fish samples collected from the Faisalabad Fish Hatchery and upstream of Chakbandi drain acted as a control. Necrosis, hemorrhage, and epithelial hyperplasia were observed in the gills of fish inhabiting the river downstream of the Chakbandi drain entrance. Liver tissues were found to be affected by vacuolated cytoplasm, bile duct proliferation, melanomacrophages, and necrosis. In kidney tissues, shrinkage of the renal cortex, necrosis, and destructive renal tubules were observed. Histopathology of muscles indicates the presence of hypertrophy and swollen myofibers. In contrast, upstream specimens of fish exhibited mild tissue alterations. Histopathology of gills tissue showed vacuolization. Liver tissues indicated the presence of hypertrophy and more frequent Kupffer cells than usual. The vacuolation was also observed in kidney tissues. Muscle tissues expressed splitting of muscle fibres and degeneration in muscle bundles. However, sections of tissues collected from farmed fish have normal morphology and no anomalies. The histopathological assessment indicated various cellular, biochemical, and histological changes in response to the contamination in the vicinity of the fish.

Assessment of hepatotoxicity and nephrotoxicity in Cirrhinus mrigala induced by trypan blue - An azo dye.

Cytotoxicity in freshwater fishes induced by industrial effluents and dyes is a global issue. Trypan blue dye has many applications in different sectors, including laboratories and industries. This study determines to detect the cytotoxic effects of trypan blue dye in vivo. The objective of this study was to estimate the sub-lethal effects of azodye in fish. Cirrhinus mrigala, a freshwater fish, was exposed to three different grading concentrations of dye 5 mg/L, 10 mg/L, and 20 mg/L in a glass aquarium. Significant (p < 0.05) decrease in the weight of fish was observed as 0.728 ± 0.14 g and 2.232 ± 0.24 g, respectively, in the trial groups exposed to 10 and 20 mg/L of dye in a week. After exposure to trypan blue dye, fishes were dissected to remove liver and kidney tissues. Histopathological assessments determined hepatotoxicity and nephrotoxicity induced by trypan blue through the paraffin wax method. This dye induces mild alterations in the liver such as congestion, hemolysis, dilated sinusoids, ruptured hepatocytes, vacuolization, edema of hepatocytes, necrosis, degeneration, aggregation, and inflammation. This dye not only alters liver tissue, also induces an acute level of tissue alterations in the kidneys, such as degeneration of epithelial cells of renal tubules, shrinkage of the glomerulus, congestion, reduced lumen, degeneration of glomerulus, absence of space of bowmen, glomerulonephritis, necrosis in hematopoietic interstitial tissues and glomerulus, reduced lumen, vacuolar degeneration of renal tubules, increased per tubular space. The current study concludes that trypan blue dye released even in small amounts is found to be associated with a high incidence of cytotoxicity. Such tissue alterations in this species could be used as biomarkers for azo dyes.

Dietary consumption of polypropylene microplastics alter the biochemical parameters and histological response in freshwater benthic mollusc Pomacea paludosa.

One of the most common environmental pollutant in aquatic ecosystems are polypropylene microplastics and their impacts on aquatic organisms are still scarce. The study aimed to prepare polypropylene microplastics using organic solvent (spherical and 11.86-44.62 µm) and then test their toxicity on the freshwater benthic mollusc grazer Pomaceae paludosa. The present study investigated chronic (28 days) exposure of polypropylene microplastics via dietary supplements (250 mg kg-1, 500 mg kg-1 & 750 mg kg-1) in P. paludosa, and the toxic effect was evaluated in digestive gland tissue. The FTIR results revealed no change in polypropylene microplastics during ingestion or after egestion. On the other hand, Ingestion causes accumulation in their bodies and disrupts redox homeostasis. Meanwhile, alteration occurs in oxidative stress-related biomarkers such as increased reactive oxygen species level (ROS), impaired the biochemical parameters of antioxidant system catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and glutathione - S- transferase (GST), deterioration of oxidative stress effects in lipid peroxidation (LPO) and carbonyl protein (CP) and changed the digestive enzymes such as amylase, pepsin, esterase and alkaline phosphatase that are measured in hepatopancreas tissue. The histology results revealed that ingesting these microplastics caused severe damage to the digestive gland cells. According to the findings, ingestion of polypropylene microplastics in benthic freshwater mollusc causes more serious harm and impacts energy acquisition. This finding represents the ecological risk of polypropylene microplastic pollution in the freshwater ecosystem.

Toxicity evaluation of polypropylene microplastic on marine microcrustacean Artemia salina: An analysis of implications and vulnerability.

Polypropylene microplastic particles are one of the predominant pollutants in marine ecosystems and their toxic effects are unknown in aquatic biota. The study aims to prepare the spherical shaped polypropylene microplastics (size range 11.86 µm-44.62 µm) and assess their toxic effects (1, 25, 50, 75 and 100 µg/mL) in various life stages (nauplii, metanauplii and juvenile) of marine microcrustacean Artemia salina within 48 h. In addition, microplastics ingestion by Artemia nauplii was proved by FTIR analysis. The results revealed, microplastics accumulation in their tract leads to change in their homeostasis, as followed increase in the oxidative burst causes mortality in nauplii (LC50 40.947 µg/mL) and meta nauplii (LC50 51.954 µg/mL). In juvenile, swimming behaviour was changed. Moreover, microplastic consumption disturbs the antioxidant biomarkers such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione -S- Transferase (GST) and reduces the neurotransmitter enzyme acetylcholinesterase (AChE) activity. In addition, histology of juvenile Artemia showed damage in epithelial cells. This study indicates that exposure to polypropylene microplastics is more harmful to zooplanktonic organisms of the marine ecosystem.

The dietary supplementation of zinc oxide and selenium nanoparticles enhance the immune response in freshwater fish Oreochromis mossambicus against aquatic pathogen Aeromonas hydrophila.

BACKGROUND: Green nanoparticles are subjected as an immunostimulant against bacterial pathogens. METHODS: Murraya koenigii berry extract-based synthesized zinc oxide nanoparticles (Mb-ZnO NPs) and selenium nanoparticles (Mb-Se NPs) were relatively analyzed for immunostimulation in serum and mucus fish Oreochromis mossambicus against Aeromonas hydrophila infections. Initial minimum inhibitory concentration (MIC) was determined for both Mb-ZnO NPs and Mb-Se NPs followed by specific growth rate (SGR), antioxidant level (Superoxide dismutase activity (SOD), Catalase activity (CA), and Glutathione peroxidase activity (GPx)), and immune parameters Myeloperoxidase activity (MPO), Respiratory burst activity (RBA), Lysozyme activity (LYZ), Alkaline phosphatase activity (ALP), Serum antiprotease activity and Natural complement activity (NAC). RESULTS: The potential bacterial inhibition property of Mb-ZnO NPs and Mb-Se NPs exhibited the most negligible concentration of 25 and 15 µg mL-1, respectively, against A. hydrophila. In addition, Mb-ZnO NPs and Mb-Se NPs exhibited 70-80 % and 90-95 % diminished biofilm activity at 50 µg mL-1 that was viewed under an inverted research microscope and confocal laser scanning microscopy (CLSM). Protein leakage and nucleic acid leakage assay quantified oozed out protein and nucleic acid from A. hydrophila that confirms Mb-Se NPs exhibited vigorous antibacterial activity than Mb-ZnO NPs at tested concentrations. Oreochromis mossambicus fed with Mb-ZnO NPs and Mb-Se NPs supplemented diet at different concentrations (0.5 mg/kg, 1 mg/kg and 2 mg/kg) improved SGR along with a rise in the immune response of those fishes against A. hydrophila infection. Serum and mucus of fish fed with Mb-Se NPs supplemented diet exhibited a significant rise in antioxidant level SOD, CA and GPx at a dosage of 2 mg/kg. Likewise, lipid peroxidation assay detected significantly diminished oxidative stress in the serum and mucus of fish fed with Mb-Se NPs supplemented diet (2 mg/kg). Enhanced immune parameters in serum and mucus of fish fed with Mb-Se NPs supplemented diet determined by MPO, RBA, LYZ, ALP, Serum antiprotease activity and NAC. CONCLUSION: Thus O. mossambicus fed with Mb-Se NPs supplemented diet was less prone to become infected by aquatic pathogen A. hydrophila established by challenge study. On the whole, Mb-Se NPs supplemented diet ensured the rise in antioxidant response that boosts the immune responses and reduces the chance of getting infected against A. hydrophila infections.

Administration of Vaccine Preservative Thimerosal Produces Impairment in Rat Liver

Abstract The present research was planned to analyze the toxic effects of thimerosal on rat liver. Mercury and mercury compounds are universally known toxicants for animals and humans. Thimerosal is widely used in the vaccines as a preservative which contains 49.6% mercury. Twenty-four adult male albino rats were distributed into four groups (n=6). The first group was considered as a control group. While, second, third and fourth groups were intoxicated with 0.5, 10 and 50 µg/kg thimerosal (i.m.) respectively. After 30 days, rats were slaughtered to analyze the liver tissues. The results of the experiment exposed that thimerosal instigated significant (p<0.05) increase in alanine transaminase (ALT), alkaline phosphatase (ALP) and aminotransferase (AST) levels. Catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) activities and Glutathione (GSH) and protein levels were significantly (p<0.05) reduced. Furthermore, significant increases in Hydrogen peroxide (H2O2), thiobarbituric acid reactive substances (TBARS) level and DNA damage was observed. Histopathological study revealed severe damages, e.g. fatty alterations, deterioration of lobular structure and degeneration of nuclei in hepatic tissues of thimerosal treated rats. Results of present investigation revealed that thimerosal induces hepatotoxicity at different levels.