Utility of zebrafish-based models in understanding molecular mechanisms of neurotoxicity mediated by the gut-brain axis.

The gut microbes perform several beneficial functions which impact the periphery and central nervous systems of the host. Gut microbiota dysbiosis is acknowledged as a major contributor to the development of several neuropsychiatric and neurological disorders including bipolar disorder, depression, anxiety, Parkinson's disease, Alzheimer's disease, attention deficit hyperactivity disorder, and autism spectrum disorder. Thus, elucidation of how the gut microbiota-brain axis plays a role in health and disease conditions is a potential novel approach to prevent and treat brain disorders. The zebrafish (Danio rerio) is an invaluable vertebrate model that possesses conserved brain and intestinal features with those of humans, thus making zebrafish a valued model to investigate the interplay between the gut microbiota and host health. This chapter describes current findings on the utility of zebrafish in understanding molecular mechanisms of neurotoxicity mediated via the gut microbiota-brain axis. Specifically, it highlights the utility of zebrafish as a model organism for understanding how anthropogenic chemicals, pharmaceuticals and bacteria exposure affect animals and human health via the gut-brain axis.

Diphenyl Diselenide Through Reduction of Inflammation, Oxidative Injury and Caspase-3 Activation Abates Doxorubicin-Induced Neurotoxicity in Rats.

Neurotoxicity associated with chemotherapy is a debilitating side effect of cancer management in humans which reportedly involves inflammatory and oxidative stress responses. Diphenyl diselenide (DPDS) is an organoselenium compound which exhibits its anti-tumoral, anti-oxidant, anti-inflammatory and anti-mutagenic effects. Nevertheless, its possible effect on chemotherapy-induced neurotoxicity is not known. Using rat model, we probed the behavioral and biochemical effects accompanying administration of antineoplastic agent doxorubicin (7.5 mg/kg) and DPDS (5 and 10 mg/kg). Anxiogenic-like behavior, motor and locomotor insufficiencies associated with doxorubicin were considerably abated by both DPDS doses with concomitant enhancement in exploratory behavior as demonstrated by reduced heat maps intensity and enhanced track plot densities. Moreover, with exception of cerebral glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, biochemical data demonstrated reversal of doxorubicin-mediated decline in cerebral and cerebellar antioxidant status indices and the increase in acetylcholinesterase (AChE) activity by both doses of DPDS. Also, cerebellar and cerebral lipid peroxidation, hydrogen peroxide as well as reactive oxygen and nitrogen species levels were considerably diminished in rats administered doxorubicin and DPDS. In addition, DPDS administration abated myeloperoxidase activity, tumour necrosis factor alpha and nitric oxide levels along with caspase-3 activity in doxorubicin-administered rats. Chemoprotection of doxorubicin-associated neurotoxicity by DPDS was further validated by histomorphometry and histochemical staining. Taken together, DPDS through offsetting of oxido-inflammatory stress and caspase-3 activation elicited neuroprotection in doxorubicin-treated rats.

Exogenous taurine administration abates reproductive dysfunction in male rats exposed to silver nanoparticles.

The broad contemporary applications of silver nanoparticles (AgNPs) have been associated with various toxicities including reproductive toxicity. Taurine is well acknowledged for its potent pharmacological role in numerous disease models and chemically-mediated toxicity. We investigated the effect of taurine on AgNPs-induced reproductive toxicity in male rats. The animals were intraperitoneally injected with AgNPs (200 µg/kg) alone or co-administered with taurine at 50 and 100 mg/kg for 21 successive days. Exogenous taurine administration significantly abated AgNPs-induced oxidative injury by decreasing the levels of oxidative stress indices while boosting antioxidant enzymes activities and glutathione level in the hypothalamus, testes and epididymis of exposed animals. Taurine administration alleviated AgNPs-induced inflammatory response and caspase-3 activity, an apoptotic biomarker. Moreover, taurine significantly improved spermiogram, reproductive hormones and the marker enzymes of testicular function in AgNPs-treated animals. The ameliorative effect of taurine on pathological lesions induced by AgNPs in the exposed animals was substantiated by histopathological data. This study provides the first mechanistic evidence that taurine supplementation affords therapeutic effect against reproductive dysfunction associated with AgNPs exposure in male rats.

Perfluorooctanoic acid induces behavioral impairment and oxidative injury in Nauphoeta cinerea nymphs.

Perfluorooctanoic acid (PFOA) is a persistent organic contaminant with potential health threats to both animals and humans. However, the impact of PFOA on insects, which play significant roles in ecosystems, is understudied. We evaluated the toxicological impact of ecologically relevant concentrations of PFOA (0, 25, 50, 100, and 200 µg L-1) on Nauphoeta cinerea nymphs following exposure for 42 consecutive days. We analyzed the behavior of the insects with automated video-tracking software and processed the head, midgut, and fat body for biochemical assays. PFOA-exposed insects exhibited significant reductions in locomotory abilities and an increase in freezing time. Furthermore, PFOA exposure reduced acetylcholinesterase activity in the insect head. PFOA exposure increased the activities of superoxide dismutase, glutathione peroxidase, and catalase in the head and midgut, but decreased them in the fat body. PFOA also significantly increased glutathione-S transferase activity, while decreasing glutathione levels in the head, midgut, and fat body. Additionally, PFOA exposure increased reactive oxygen and nitrogen species, nitric oxide, lipid peroxidation, and protein carbonyl contents in the head, midgut, and fat body of the insects. In conclusion, our findings indicate that PFOA exposure poses an ecological risk to Nauphoeta cinerea.

Atrazine: cytotoxicity, oxidative stress, apoptosis, testicular effects and chemopreventive Interventions.

Atrazine (ATZ) is an environmental pollutant that interferes with several aspects of mammalian cellular processes including germ cell development, immunological, reproductive and neurological functions. At the level of human exposure, ATZ reduces sperm count and contribute to infertility in men. ATZ also induces morphological changes similar to apoptosis and initiates mitochondria-dependent cell death in several experimental models. When in vitro experimental models are exposed to ATZ, they are faced with increased levels of reactive oxygen species (ROS), cytotoxicity and decreased growth rate at dosages that may vary with cell types. This results in differing cytotoxic responses that are influenced by the nature of target cells, assay types and concentrations of ATZ. However, oxidative stress could play salient role in the observed cellular and genetic toxicity and apoptosis-like effects which could be abrogated by antioxidant vitamins and flavonoids, including vitamin E, quercetin, kolaviron, myricetin and bioactive extractives with antioxidant effects. This review focuses on the differential responses of cell types to ATZ toxicity, testicular effects of ATZ in both in vitro and in vivo models and chemopreventive strategies, so as to highlight the current state of the art on the toxicological outcomes of ATZ exposure in several experimental model systems.

Cellular and molecular mechanisms of aflatoxin B1-mediated neurotoxicity: The therapeutic role of natural bioactive compounds.

Aflatoxin B1 (AFB1), a dietary toxin from the mold Aspergillus species, is well acknowledged to elicit extra-hepatic toxicity in both animals and humans. The neurotoxicity of AFB1 has become a global public health concern. Contemporary research on how AFB1 enters the brain to elicit neuronal dysregulation leading to noxious neurological outcomes has increased greatly in recent years. The current review discusses several neurotoxic outcomes and susceptible targets of AFB1 toxicity at cellular, molecular and genetic levels. Specifically, neurotoxicity studies involving the use of brain homogenates, neuroblastoma cell line IMR-32, human brain microvascular endothelial cells, microglial cells, and astrocytes, as well as mammalian and non-mammalian models to unravel the mechanisms associated with AFB1 exposure are highlighted. Further, some naturally occurring bioactive compounds with compelling therapeutic effects on AFB1-induced neurotoxicity are reviewed. In conclusion, available data from literature highlight AFB1 as a neurotoxin and its possible pathological contribution to neurological disorders. Further mechanistic studies aimed at discovering and developing effective therapeutics for AFB1 neurotoxicity is warranted.

Metoprolol elicits neurobehavioral insufficiency and oxidative damage in nontarget Nauphoeta cinerea nymphs.

Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental matrices globally. The dwindling in the biodiversity of useful insects owing to increasing presence of environmental chemicals is currently a great interest to the scientific community. In the current research, the toxicological impact of ecologically relevant concentrations of metoprolol at 0, 0.05, 0.1, 0.25, and 0.5 µg/L on Nauphoeta cinerea nymphs following exposure for 42 consecutive days was evaluated. The insects' behavior was analyzed with automated video-tracking software (ANY-maze, Stoelting Co, USA) while biochemical assays were done using the midgut, head and fat body. Metoprolol-exposed nymphs exhibited significant diminutions in the path efficiency, mobility time, distance traveled, body rotation, maximum speed and turn angle cum more episodes, and time of freezing. In addition, the heat maps and track plots confirmed the metoprolol-mediated wane in the exploratory and locomotor fitness of the insects. Compared with control, metoprolol exposure decreased acetylcholinesterase activity in insects head. Antioxidant enzymes activities and glutathione level were markedly decreased whereas indices of inflammation and oxidative injury to proteins and lipids were significantly increased in head, midgut and fat body of metoprolol-exposed insects. Taken together, metoprolol exposure induces neurobehavioral insufficiency and oxido-inflammatory injury in N. cinerea nymphs. These findings suggest the potential health effects of environmental contamination with metoprolol on ecologically and economically important nontarget insects.

Co-administration of thymol and sulfoxaflor impedes the expression of reproductive toxicity in male rats.

This study investigated the capability of a co-delivery system of thymol (THY) and sulfoxaflor that can serve to minimize the development of epididymal and testicular injury arise from SFX exposures alone. Forty-eight adult male rats were orally treated by gavage for 28 consecutive days. The rats were divided into six groups comprising control, THY alone (30 mg/kg), low SFX alone (79.4 mg/kg), high SFX alone (205 mg/kg) and co-exposure groups. After euthanasia, the rats epididymal and testicular damage and antioxidant status markers, myeloperoxidase (MPO) activity, levels of nitric oxide, total antioxidant capacity (TAC), total oxidative stress (TOS) and lipid peroxidation (LPO) were analyzed. Levels of tumor necrosis factor alpha (TNF-α), interleukin-1 b (IL-1ß) and caspase-3 activity were assessed using ELISA kits. The results revealed that SFX exposure caused a significant (p < 0.05) decrease in the body weight, sperm functional parameters, serum testosterone level with widespread histological abnormalities in a dose-dependent manner. Increased relative organ weights, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were observed in low SFX-treated rats. Similarly, the epididymal and testicular myeloperoxidase activity, malondialdehyde (MDA), reactive oxygen species (RONS), tumor necrosis-α, interleukin-1ß levels and caspase-3 activity were significant (p < 0.05) increased and a significant (p < 0.05) reduction in antioxidant enzyme activities and reduced glutathione (GSH) were revealed in SFX-treated rats. However, co-treatment of THY with SFX prevented SFX-induced epididymal and testicular toxicities. Thus, thymol protected against potential epididymis and testes alterations elicited by oxido-inflammatory mediators and up regulated antioxidant status.

Neurotoxicity of furan in juvenile Wistar rats involves behavioral defects, microgliosis, astrogliosis and oxidative stress.

Evidence suggests that furan, a widespread environmental and food contaminant, causes liver toxicity and cancer, but its implications in the brain are not well defined. We measured behavioral, glial, and biochemical responses in male juvenile rats exposed orally to 2.5, 5 and 10 mg/kg furan and vitamin E after 28 days. Furan-mediated hyperactivity peaked at 5 mg/kg and did not exacerbate at 10 mg/kg. Enhanced motor defect was also observed at 10 mg/kg. Furan-treated rats elicited inquisitive exploration but showed impaired spatial working memory. Without compromising the blood-brain barrier, furan induced glial reactivity with enhanced phagocytic activity, characterized by parenchyma-wide microglial aggregation and proliferation, which switched from hyper-ramified to rod-like morphology with increasing doses. Furan altered the glutathione-S-transferase-driven enzymatic and non-enzymatic antioxidant defence systems differentially and dose-dependently across brain regions. Redox homeostasis was most perturbed in the striatum and least disrupted in hippocampus/cerebellum. Vitamin E supplementation attenuated exploratory hyperactivity and glial reactivity but did not affect impaired working memory and oxidative imbalance. Overall, sub-chronic exposure of juvenile rats to furan triggered glial reactivity and behavioral deficits suggesting the brain's vulnerability during juvenile development to furan toxicity. It remains to be determined whether environmentally relevant furan concentrations interfere with critical brain developmental milestones.

Amelioration of neurobehavioral, biochemical, and morphological alterations associated with silver nanoparticles exposure by taurine in rats.

The adverse effect of silver nanoparticles (AgNPs) on the nervous system is an emerging concern of public interest globally. Taurine, an essential amino acid required for neurogenesis in the nervous system, is well-documented to possess antioxidant, anti-inflammatory, and antiapoptotic activities. Yet, there is no report in the literature on the effect of taurine on neurotoxicity related to AgNPs exposure. Here, we investigated the neurobehavioral and biochemical responses associated with coexposure to AgNPs (200 µg/kg body weight) and taurine (50 and 100 mg/kg body weight) in rats. Locomotor incompetence, motor deficits, and anxiogenic-like behavior induced by AgNPs were significantly alleviated by both doses of taurine. Taurine administration enhanced exploratory behavior typified by increased track plot densities with diminished heat maps intensity in AgNPs-treated rats. Biochemical data indicated that the reduction in cerebral and cerebellar acetylcholinesterase activity, antioxidant enzyme activities, and glutathione level by AgNPs treatment were markedly upturned by both doses of taurine. The significant abatement in cerebral and cerebellar oxidative stress indices namely reactive oxygen and nitrogen species, hydrogen peroxide, and lipid peroxidation was evident in rats cotreated with AgNPs and taurine. Further, taurine administration abated nitric oxide and tumor necrosis factor-alpha levels cum myeloperoxidase and caspase-3 activities in AgNPs-treated rats. Amelioration of AgNPs-induced neurotoxicity by taurine was confirmed by histochemical staining and histomorphometry. In conclusion, taurine via attenuation of oxido-inflammatory stress and caspase-3 activation protected against neurotoxicity induced by AgNPs in rats.

Attenuation of doxorubicin-induced hypothalamic-pituitary-testicular axis dysfunction by diphenyl diselenide involves suppression of hormonal deficits, oxido-inflammatory stress and caspase 3 activity in rats.

BACKGROUND: Doxorubicin (DOX) is one of the popular anti-cancer drugs in the world and several literatures have implicated it in various toxicities especially cardiotoxicity and reproductive toxicity. Diphenyl diselenide (DPDS) is well acknowledged for its compelling pharmacological effects in numerous disease models and chemically-mediated toxicity. This study was carried out to investigate the effect of DPDS on DOX-induced changes in the reproductive indices of male Wistar rats. METHODS: Rats were intraperitoneally injected with 7.5 mg/kg body weight of DOX alone once followed by treatment with DPDS at 5 and 10 mg/kg for seven successive days. Excised hypothalamus, testes and epididymis were processed for biochemical and histological analyses. RESULTS: DPDS treatment significantly (p < 0.05) abated DOX-induced oxidative damage by decreasing the levels of oxidative stress indices such as hydrogen peroxide, reactive oxygen and nitrogen species, and lipid peroxidation with a respective improvement in the level of glutathione in the hypothalamic, testicular and epididymal tissues of DOX-treated rats. The activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione S-transferase and glutathione peroxidase were upregulated in the DPDS co-treated group. DPDS co-treatment alleviates the burden of DOX-induced inflammation by significant reductions in myeloperoxidase activity, levels of nitric oxide and tumor necrosis factor alpha with concomitant decline in the activity of caspase-3, an apoptotic biomarker. Consequently, significant improvement in the spermiogram, levels of reproductive hormones (follicle stimulating hormone, luteinizing hormone, prolactin, serum testosterone and intra-testicular testosterone) levels in the DPDS co-treatment group in comparison to DOX alone-treated group were observed. Histology results of the testes and epididymis showed that DPDS significantly alleviated pathological lesions induced by DOX in the animals. CONCLUSION: DPDS may modulate reproductive toxicity associated with DOX therapy in male cancer patients.

Persistent oxidative injury and neurobehavioral impairment in adult male and female Nauphoeta cinerea exposed to perfluorooctanoic acid.

This study aimed to elucidate if the toxicity of perfluorooctanoic acid (PFOA), an emerging persistent organic contaminant, is reversible or not in adult male and female Nauphoeta cinerea. Both sexes of Nauphoeta cinerea were separately exposed to 0, 1 and 5 mg/L PFOA in drinking water for 21 consecutive days. PFOA-exposed Nauphoeta cinerea exhibited significant deficits in the locomotor and exploratory capabilities with concomitant increase in anxiogenic behaviors which persisted after cessation of PFOA exposure. Moreover, PFOA-induced decrease in acetylcholinesterase activity persisted after cessation of PFOA exposure in both insects' sexes. Catalase and superoxide dismutase activities were increased in the midgut but restored to control following cessation of PFOA exposure. The increased reactive oxygen and nitrogen species, nitric oxide and hydrogen peroxide levels persisted in the head whereas they were abated in the midgut after cessation of PFOA exposure. However, PFOA-induced persistent increase in lipid peroxidation and protein carbonyl levels in the head and midgut of insects. Collectively, PFOA exposure elicited persistent neurobehavioral and oxidative injury similarly in both sexes of adult Nauphoeta cinerea during this investigation.

Kolaviron modulates angiogenesis, apoptosis and inflammatory signaling in rat model of testosterone propionate-induced benign prostate hyperplasia.

Benign prostatic hyperplasia (BPH) is a non-malignant disease of the prostate characterized by uncontrolled proliferation of the prostate gland. Inflammation and oxidative stress have been reported to play a role in the development of BPH. Kolaviron, a bioflavonoid complex of Garcinia kola seed, has been shown to possess anti-inflammatory effect. In this study, we investigated the effect of Kolaviron on testosterone propionate (TP)-induced BPH in rats. Fifty male rats were assigned in 5 groups. Groups 1 and 2 were orally exposed to corn oil (2 ml/kg) and Kolaviron (200 mg/kg/day, p.o) for 28 days. Group 3 rats received TP (3 mg/kg/day, s.c) for 14 days while Groups 4 and 6 were treated with Kolaviron (200 mg/kg/day, p.o) and Finasteride (5 mg/kg/day, p.o), respectively, for 14 days prior to TP (3 mg/kg, s.c) co-exposure for the remaining 14 days. Administration of Kolaviron to TP-treated rats reverted histological alteration and significantly decreased prostate weight, prostate index, 5α-reductase, dihydrotestosterone, androgen receptor expression, tumor necrosis factor α, interleukin-1ß, cyclooxygenase-2, prostaglandin E2, 5-lipoxygenase leukotriene B4, inducible nitric oxide synthase and nitric oxide concentration. In addition, Kolaviron alleviated TP-induced oxidative stress and reduced the expression of Ki-67, VEGF, and FGF to almost control levels. Furthermore, Kolaviron promoted apoptosis in TP-treated rats through downregulation of BCL-2 and upregulation of P53 and Caspase 3 expressions. Overall, Kolaviron prevented BPH via regulation of androgen/androgen receptor signaling, anti-oxidative and anti-inflammatory mechanisms.

Thymol co-administration abrogates hexachlorobenzene-induced reproductive toxicities in male rats.

This present study was designed to investigate ameliorating potential of thymol (THY) on hexachlorobenzene (HBC)-induced epididymal and testicular toxicities in adult male rats. Forty adult male rats were orally treated by gavage daily for 28 consecutive days and divided into four groups; control group administered with corn oil, HBC-treated group (16 mg/kg b. wt), thymol-treated group (30 mg/kg b. wt), and HBC + THY-treated group. The results revealed that HBC exposure caused a significant decrease in the body weight change, organ weights, sperm functional parameters, serum testosterone level with widespread histological abnormalities. Furthermore, HBC-treated rats showed increased in the serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), epididymal and testicular myeloperoxidase activity, tumor necrosis-α, interleukin-1ß level and caspase-3 activity, induced oxidative damage as evidenced by elevated malondialdehyde (MDA), reactive oxygen species (RONS) levels and significant reduction in antioxidant enzyme activities and reduced glutathione (GSH). However, co-treatment of THY with HBC alleviated the HBC-induced epididymal and testicular toxicities. Our findings revealed that HBC acts as a reproductive toxicant in rats and thymol could be a potential remedial agent for HBC-induced reproductive toxicity.

Dietary myricetin assuages atrazine-mediated hypothalamic-pituitary-testicular axis dysfunction in rats.

Atrazine (ATZ) exposure is associated with reproductive dysfunction in both animals and humans. Myricetin, a flavonoid compound, is well documented for its numerous pharmacological activities. However, the impact of myricetin on the atrazine-mediated dysfunctional hypothalamic-pituitary-testicular axis is not known. This study investigated the role of myricetin on the atrazine-induced alterations in the male reproductive axis in rats orally gavaged with ATZ alone (50 mg/kg) or co-treated with ATZ + myricetin (MYR) at 5, 10, and 20 mg/kg for 30 consecutive days. Myricetin assuaged ATZ-induced reductions in intra-testicular testosterone, serum follicle-stimulating hormone, luteinizing hormone, and testosterone, coupled with decreases in alkaline phosphatase, acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activities. Also, MYR treatment improved epididymal sperm count and motility and decreased sperm defects in ATZ-treated rats. Testicular sperm number, daily sperm production, and sperm viability remained unchanged in all treatment groups. Administration of MYR abated ATZ-mediated depletion in antioxidant status, an increase in myeloperoxidase activity, nitric oxide, hydrogen peroxide, malondialdehyde levels, and reactive oxygen and nitrogen species, as well as the histological lesions in the hypothalamus, epididymis, and testes of treated animals. All in all, MYR mitigated atrazine-mediated functional changes in the reproductive axis via anti-inflammatory and antioxidant mechanisms in atrazine-exposed rats. Dietary intake of MYR could be a worthy chemoprotective approach against reproductive dysfunction related to ATZ exposure.

Molecular mechanisms associated with the chemoprotective role of protocatechuic acid and its potential benefits in the amelioration of doxorubicin-induced cardiotoxicity: A review.

Since its discovery in the 1960 s, doxorubicin (DOX) has constantly elicited the broadest spectrum of cancerocidal activity against human cancers. However, cardiotoxicity caused by DOX directly as well as its metabolites is a great source of concern over the continuous use of DOX in chemotherapy. While the exact mechanism of DOX-induced cardiotoxicity is yet to be completely understood, recent studies indicate oxidative stress, inflammation, and several forms of cell death as key pathogenic mechanisms that underpin the etiology of doxorubicin-induced cardiotoxicity (DIC). Notably, these key mechanistic events are believed to be negatively regulated by 3,4-dihydroxybenzoic acid or protocatechuic acid (PCA)-a plant-based phytochemical with proven anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Here, we review the experimental findings detailing the potential ameliorative effects of PCA under exposure to DOX. We also discuss molecular insights into the pathophysiology of DIC, highlighting the potential intervention points where the use of PCA as a veritable chemoprotective agent may ameliorate DOX-induced cardiotoxicities as well as toxicities due to other anticancer drugs like cisplatin. While we acknowledge that controlled oral administration of PCA during chemotherapy may be insufficient to eliminate all toxicities due to DOX treatment, we propose that the ability of PCA to block oxidative stress, attenuate inflammation, and abrogate several forms of cardiomyocyte cell death underlines its great promise in the amelioration of DIC.

Utility of cockroach as a model organism in the assessment of toxicological impacts of environmental pollutants.

Environmental pollution is a global concern because of its associated risks to human health and ecosystem. The bio-monitoring of environmental health has attracted much attention in recent years and efforts to minimize environmental contamination as well as to delineate toxicological mechanisms related to toxic exposure are essential to improve the health conditions of both humans and animals. This review aims to substantiate the need and advantages in utilizing cockroaches as a complementary, non-mammalian model to further understand the noxious impact of environmental contaminants on humans and animals. We discuss recent advances in neurotoxicology, immunotoxicology, reproductive and developmental toxicology, environmental forensic entomotoxicology, and environmental toxicology that corroborate the utility of the cockroach (Periplaneta americana, Blaptica dubia, Blattella germanica and Nauphoeta cinerea) in addressing toxicological mechanisms as well as a sensor of environmental pollution. Indeed, recent improvements in behavioural assessment and the detection of potential biomarkers allow for the recognition of phenotypic alterations in cockroaches following exposure to toxic chemicals namely saxitoxin, methylmercury, polychlorinated biphenyls, electromagnetic fields, pharmaceuticals, polycyclic aromatic hydrocarbon, chemical warfare agents and nanoparticles. The review provides a state-of-the-art update on the current utility of cockroach models in various aspects of toxicology as well as discusses the potential limitations and future perspectives.

Induction of aggression and anxiety-like responses by perfluorooctanoic acid is accompanied by modulation of cholinergic- and purinergic signaling-related parameters in adult zebrafish.

Perfluorooctanoic acid (PFOA) is a contaminant of global concern owing to its prevalent occurrence in aquatic and terrestrial environments with potential hazardous impact on living organisms. Here, we investigated the influence of realistic environmental concentrations of PFOA (0, 0.25, 0.5, or 1.0 mg/L) on relevant behaviors of adult zebrafish (Danio rerio) (e.g., exploration to novelty, social preference, and aggression) and the possible role of PFOA in modulating cholinergic and purinergic signaling in the brain after exposure for 7 consecutive days. PFOA significantly increased geotaxis as well as reduced vertical exploration (a behavioral endpoint for anxiety), and increased the frequency and duration of aggressive episodes without affecting their social preference. Exposure to PFOA did not affect ADP hydrolysis, whereas ATP and AMP hydrolysis were significantly increased at the highest concentration tested. However, AChE activity was markedly decreased in all PFOA-exposed groups when compared with control. In conclusion, PFOA induces aggression and anxiety-like behavior in adult zebrafish and modulates both cholinergic and purinergic signaling biomarkers. These novel data can provide valuable insights into possible health threats related to human activities, demonstrating the utility of adult zebrafish to elucidate how PFOA affects neurobehavioral responses in aquatic organisms.

Pterocarpus mildbraedii leaf extract ebbs propanil-induced oxidative and apoptotic damage in the liver of rats.

Phytochemicals derived from plant sources are well recognized as sources of pharmacologically potent drugs in the treatment of several oxidative stress-related ailments. Dichloromethane/methanol (1:1) leaf extract of Pterocarpus mildbraedii was evaluated for its possible protection against oxidative stress and apoptosis in the liver of male Wistar rats exposed to propanil (PRP). In the experimental design, olive oil served as the vehicle, and rats were grouped into control (2 mL/kg olive oil), PRP (200 mg/kg/day), Pterocarpus mildbraedii extract (200 mg/kg/day), and Pterocarpus mildbraedii extract (200 mg/kg/day)+PRP (200 mg/kg/day), and treated daily, p.o., for seven days. Oxidative stress parameters, B-cell lymphoma 2 (Bcl-2), Bcl 2-associated X protein (Bax), p53, caspases (9/3), and terminal transferase dUTP nick end labeling (TUNEL) assays were observed in all groups. Propanil significantly elevated superoxide dismutase and lipid peroxidation levels, while concomitantly depleting GSH and p53 levels. Further, PRP enhanced the expressions of caspase-9, caspase-3, Bax, and TUNEL-positive cells in the liver of rats. However, these observed alterations were reversed following treatment with Pterocarpus mildbraedii extract. Our studies suggest that Pterocarpus mildbraedii extract protected against PRP toxicity by reducing oxidative stress and attenuating critical endpoints in the intrinsic apoptotic pathway.