Biochemistry
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Item Influence of acid-sensing ion channel blocker on behavioral responses in a zebrafish model of acute visceral pain(Elsevier B.V., 2022) Adedara, I. A.; Costa, F. V.; Biasuz, E.; Canzian, J.; Farombi, E. O.; Rosemberg, D. B.Acid-sensing ion channels (ASICs) play significant roles in numerous neurological and pathological conditions, including pain. Although acid-induced nociception has been characterized previously in zebrafish, the contri- bution of ASICs in modulating pain-like behaviors is still unknown. Here, we investigated the role of amiloride, a nonselective ASICs blocker, in the negative modulation of specific behavioral responses in a zebrafish-based model of acute visceral pain. We verified that intraperitoneal injection (i.p.) of 0.25, 0.5, 1.0, and 2.0 mg/mL amiloride alone or vehicle did not change zebrafish behavior compared to saline-treated fish. Administration of 2.5% acetic acid (i.p.) elicited writhing-like response evidenced by the abnormal body curvature and impaired locomotion and motor activity. Attenuation of acetic acid-induced pain was verified at lower amiloride doses (0.25 and 0.5 mg/mL) whereas 1.0 and 2.0 mg/mL abolished pain-like responses. The protective effect of the highest amiloride dose tested was evident in preventing writhing-like responses and impaired locomotion and vertical activity. Collectively, amiloride antagonized abdominal writhing-like phenotype and aberrant behaviors, supporting the involvement of ASICs in a zebrafish-based model of acute visceral painItem Utility of cockroach as a model organism in the assessment of toxicological impacts of environmental pollutants(Elsevier Ltd., 2022) Adedara, I. A.; Mohammed, K. A.; Da-Silva, O. F.; Salaudeen, F. A.; Goncalves, F. L. S.; Rosemberg, D. B.; Aschner, M.; Rocha, J. B. T.; Farombi, E. O.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 neuro- toxicology, immunotoxicology, reproductive and developmental toxicology, environmental forensic entomo- toxicology, 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, pharma- ceuticals, 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.Item Kolaviron suppresses dysfunctional reproductive axis associated with multi-walled carbon nanotubes exposure in male rats(Springer-Verlag GmbH, 2021) Adedara, I. A.; Awogbindin, I. O.; Maduako, I. C.; Ajeleti, A. O.; Owumi, S. E.; Owoeye, O.; Patlola, A. K.; Farombi, E. O.Reproductive toxicity associated with excessive exposure to multi-walled carbon nanotubes (MWCNTs), which are commonly used in medicine as valuable drug delivery systems, is well documented. Kolaviron, a bioflavonoid isolated from Garcinia kola seeds, elicits numerous health beneficial effects related to its anti-inflammatory, anti-genotoxic activities, anti-apoptotic, and antioxidant properties. However, information on the role of kolaviron inMWCNTs-induced reproductive toxicity is not available in the literature. Herein, we assessed the protective effects of kolaviron onMWCNTs-induced dysfunctional reproductive axis in rats following exposure toMWCNTs (1 mg/kg) and concurrent treatment with kolaviron (50 or 100 mg/kg body weight) for 15 successive days. Results showed thatMWCNTs-induced dysfunctional reproductive axis as evidenced by deficits in pituitary and testicular hormones, marker enzymes of testicular function, and sperm functional characteristics were abrogated in rats coadministered with kolaviron. Moreover, co-administration of kolaviron-abated MWCNTs-induced inhibition of antioxidant enzyme activities increases in oxidative stress and inflammatory indices. This is evidenced by diminished levels of tumor necrosis factor-alpha, nitric oxide, lipid peroxidation, reactive oxygen, and nitrogen species as well as reduced activity of myeloperoxidase in testes, epididymis, and hypothalamus of the rats. Biochemical data on the chemoprotection of MWCNTsinduced reproductive toxicity were corroborated by histological findings. Taken together, kolaviron suppressed dysfunctional reproductive axis associated with MWCNTs exposure via abrogation of oxidative stress and inflammation in male rats.Item Neuroprotective role of gallic acid in aflatoxin Bi-induced behavioral abnormalities in rats(Wiley Periodicals LLC, 2020) Adedara, I. A.; Owumi, S. E.; Oyelere, A. K.; Farombi, E. O.The neurotoxic impact of dietary exposure to aflatoxin Bi (AFBJ is documented in experimental and epidemiological studies. Gallic acid (GA) is a triphenolic phyto- chemical with potent anticancer, anti-inflammatory, and antioxidant activities. There is a knowledge gap on thè influence of GA on AFBi-induced neurotoxicity. This study probed thè influence of GA on neurobehavioral and biochemical abnormalities in rats orally treated with AFBi per se (75pg/kg body weight) or administered together with GA (20 and 40mg/kg) for 28 uninterrupted days. Behavioral endpoints obtained with video-tracking software demonstrated sig-nificant (p<.05) abatement of AFBrinduced anxiogenic-like behaviors (increased freezing, urination, and fecal bolus discharge), motor and locomotor inadequacies, namely increased negative geotaxis and diminished grip strength, absolute turn angle, total time mobile, body rotation, maximum speed, and total distance traveled by GA. The improvement of exploratory behavior in animals that received both AFBi and GA was confirmed by track plots and heat maps appraisal. Abatement of AFBj-induced decreases in acetylcholinesterase activity, antioxidant status and glutathione level by GA was accompanied by a marked reduction in oxidative stress markers in thè cerebellum and cerebrum of rats. Additionally, GA treatment abro- gated AFBi-mediated decrease in interleukin-10 and elevation of inflammatory in- dices, namely tumor necrosis factor-a, myeloperoxidase activity, interleukin-l|3, and nitric oxide. Further, GA treatment curtailed caspase-3 activation and histological injuries in thè cerebral and cerebellar tissues. In conclusion, abatement of AFBi-induced neurobehavioral abnormalities by GA involves anti-inflammatory, antioxidant, and antiapoptotic mechanisms in rats.Item Chronic ciprofloxacin and atrazine co-exposure aggravates locomotor and exploratory deficits in non-target detritivore speckled cockroach (Nauphoeta cinerea)(Springer-Verlag GmbH, 2021) Adedara, I. A. || || || || || || ||; Godswill, U. S.; Mike. M. A.; Afolabi, B. A.; Amorha, C. C.; Sule, J.; Rocha, J. B. T.; Farombi, E. O.The global detection of ciprofloxacin and atrazine in soil is linked to intensive anthropogenic activities in agriculture and inadvertent discharge of industrial wastes to the environment. Nauphoeta cinerea is a terrestrial insect with cosmopolitan distribution and great environmental function. The current study probed the neurobehavioral and cellular responses of N. cinerea singly and jointly exposed to atrazine (1.0 and 0.5 μg g−1 feed) and ciprofloxacin (0.5 and 0.25 μg g−1 feed) for 63 days. Results demonstrated that the reductions in the body rotation, maximum speed, turn angle, path efficiency, distance traveled, episodes, and time of mobility induced by atrazine or ciprofloxacin per se was exacerbated in the co-exposure group. The altered exploratory and locomotor in insects singly and jointly exposed to ciprofloxacin and atrazine were verified by track plots and heat maps. Furthermore, we observed a decrease in acetylcholinesterase and anti-oxidative enzyme activities with concomitant elevation in the levels of lipid peroxidation, nitric oxide, and reactive oxygen and nitrogen species were significantly intensified in the midgut, hemolymph, and head of insects co-exposed to ciprofloxacin and atrazine. In conclusion, exposure to binary mixtures of ciprofloxacin and atrazine elicited greater locomotor and exploratory deficits than upon exposure to the individual compound by inhibiting acetylcholinesterase activity and induction of oxido-inflammatory stress responses in the insects. N. cinerea may be a usable model insect for checking contaminants of ecological risks.Item Abatement of the dysfunctional hypothalamic–pituitary–gonadal axis due to ciprofloxacin administration by selenium in male rats(Wiley Periodicals LLC, 2021) Adedara, I. A.; Awogbindin, I. O.; Mohammed, K. A.; Da-Silva, O. F.; Farombi, E. O.The present study examined the influence of selenium on ciprofloxacin‐mediated reproductive dysfunction in rats. The research design consisted of five groups of eight animals each. The rats were administered 135 mg/kg body weight of ciprofloxacin per se or simultaneously with selenium at 0.25 and 0.5 mg/kg for 15 uninterrupted days. Antioxidant and inflammatory indices were assayed using the testes, epididymis, and hypothalamus of the animals after sacrifice. Results revealed that ciprofloxacin treatment per se interfered with the reproductive axis as demonstrated by diminished serum hormonal levels, sperm quality, and enzymatic indices of testicular function, which were, however, abrogated following selenium co‐treatment. Besides this, administration of selenium attenuated the depletion of glutathione level, inhibition of catalase, superoxide dismutase, glutathione‐Stransferase and glutathione peroxidase activities with a concomitant reduction in reactive oxygen and nitrogen species, and lipid peroxidation in ciprofloxacintreated in rats. Selenium treatment also mitigated ciprofloxacin‐mediated elevation in nitric oxide level and of myeloperoxidase activity as well as histological lesions in the animals. Overall, selenium attenuated impairment in the male reproductive axis due to ciprofloxacin treatment through abatement of inflammation and oxidative stress in rats.Item Toxicological outcome of exposure to psychoactive drugs carbamazepine and diazepam on non-target insect Nauphoeta cinerea(Elsevier Ltd., 2021) Adedara, I. A.; Ajayi, B. O.; Afolabi, B. A.; Awogbindin, I. O.; Rocha, J. B. T.; Farombi, E. O.The continuous detection of human pharmaceuticals during environmental biomonitoring is a global concern because of thè menaces they may exert on non-target organisms. Carbamazepine (CBZ) and diazepam (DZP) are commonly prescribed psychotropic drugs which have been reported to coexist in thè environment globally. Nauphoeta cinerea is a common insect with high ecological impact. This study elucidated thè influence of co-exposure to DZP (0.5 and 1.0 pg kg-1 diet) and CBZ (1.5 and 3.0 pg kg~* diet) for 42 days on thè behavior and biochemical responses in Nauphoeta cinerea. Results showed that DZP alone did not induce adverse effect on thè behavior and antioxidant status in thè exposed insects. However, exposure to CBZ alone and binary mixtures of DZP and CBZ significantly decreased locomotor and exploratory accomplishments evidenced by decreased mobile episodes, total mobile time, maximum speed, total distance traveled, absolute turn angle, body rotation and path efficiency in comparison with control. The decline observed in thè exploratory activities of insects fed with CBZ alone and thè mixtures was confirmed by tracie plots and heat maps. Further, acetylcholinesterase and antioxidant enzyme activities decreased significantly whereas reactive oxygen and nitrogen species, nitric oxide and lipid peroxidation levels increased significantly in thè hemolymph, head and midgut of insects exposed to CBZ alone and thè mixtures. Collectively, CBZ alone and binary mixtures of CBZ and DZP .Item Hazardous impact of diclofenac exposure on thè behavior and antioxidant defense System in Nauphoeta cinerea(Elsevier Ltd., 2020) Adedara, I. A.; Awogbindin, I. O.; Afolabi, B. A.; Ajayi, B. O.; Rocha, J. B. T.; Farombi, E. O.Environmental pollution by pharmaceuticals such as diclofenac (DCF) is globally acknowledged to be a threat to thè ecosystems. Nauphoeta cinerea is an important insect with valuable ecological role. The present investigation aimed to elucidate thè impact of DCF on insects by assessing thè behavior and antioxidant defense response in nymphs ofN. cinerea exposed to DCF-contaminated food at 0,0.5,1.0 and 2.0 pg kg~* feed for 42 successive days. Subsequent to exposure period, neurobehavioral analysis using video-tracking software in a novel apparatus was performed before estimation of biochemical endpoints in thè head, midgut and hemolymph of thè insects. Results indicated that DCF-exposed insects exhibited marked reduction in thè maximum speed, total distance traveled, mobile episodes, total mobile time, body rotation, absolute turn angle and path efficiency, whereas thè total freezing time was increased compared with thè control. The diminution in thè exploratory activities of DCF-exposed insects was substantiated by heat maps and track plots. Additionally, DCF elicited marked diminution in antioxidant enzyme and acetylcholinesterase (AChE) activities along with increase in nitric oxide (NO), reactive oxygen and nitrogen species (RONS), and lipid peroxidation (LPO) levels in thè head, midgut and hemolymph of thè insects. Taken together, DCF elicited neurotoxicity and oxido-inflammatory stress in exposed insects. N. cinerea may be a suitable model insect for environmental risk assessment of pharmaceuticals in non-target insect species.Item Neurobehavioural and biochemical responses associated with exposure to binary waterborne mixtures of zinc and nickel in rats(1382-6689, 2020) Adedara, I. A.; Adegbosin, A. N.; Owoeye, O.; Abiola, M. A.; Odunewu, A. A.; Owoeye, O.; Owumi, S. E.; Farombi, E. O.Environmental and occupational exposure to metal mixtures due to various geogenic and anthropogenic ac- tivities poses a health threat to exposed organisms. The outcome of systemic interactions of metals is a topical area of research because it may cause either synergistic or antagonistic effect. The present study investigated the impact of co-exposure to environmentally relevant concentrations of waterborne nickel (75 and 150 pg NiCl 2L-1) and zinc (100 and 200pg ZnC^L-1) mixtures on neurobehavioural performance of rats. Locomotor, motor and exploratory activities were evaluated using video-tracking software during trial in a novel arena and thereafter, biochemical and histological analyses were performed using the cerebrum, cerebellum and liver. Results indicated that zinc significantly (p < 0.05) abated the nickel-induced locomotor and motor deficits as well as improved the exploratory activity of exposed rats as verified by track plots and heat map analyses. Moreover, zinc mitigated nickel-mediated decrease in acetylcholinesterase activity, elevation in biomarkers of liver damage, levels of reactive oxygen and nitrogen species as well as lipid peroxidation in the exposed rats when compared with control. Additionally, nickel mediated decrease in antioxidant enzyme activities as well as the increase in tumour necrosis factor alpha, interleukin-1 beta and caspase-3 activity were markedly abrogated in the cerebrum, cerebellum and liver of rats co-exposed to nickel and zinc. Histological and histomorphome- trical analyses evinced that zinc abated nickel-mediated neurohepatic degeneration as well as quantitative re- duction in the widest diameter of the Purkinje cells and the densities of viable granule cell layer of dentate gyrus, pyramidal neurones of cornu ammonis 3 and cortical neurons in the exposed rats. Taken together, zinc abrogated nickel-induced neurohepatic damage via suppression of oxido-inflammatory stress and caspase-3 activation in rats.Item Kolaviron via anti-inflammatory and redox regulatory mechanisms abates multi-walled carbon nanotubes-induced neurobehavioral deficits in rats(Springer-Verlag GmbH, 2020) Adedara, I. A.; Awogbindin, I. O.; Owoeye, O.; Maduako, I. C.; Ajeleti, A. O.; Owumi, S. E.; Patlola, A. K.; Farombi, E. O.Exposure to multi-walled carbon nanotubes (MWCNTs) reportedly elicits neurotoxic effects. Kolaviron is a phytochem- ical with several pharmacological effects namely anti-oxidant, anti-inflammatory, and anti-genotoxic activities. The present study evaluated the neuroprotective mechanism of kolaviron in rats intraperitoneally injected with MWCNTs alone at 1 mg/kg body weight or orally co-administered with kolaviron at 50 and 100 mg/kg body weight for 15 consecutive days. Following exposure, neurobehavioral analysis using video-tracking software during trial in a novel environment indicated that co-administration of both doses of kolaviron significantly (p < 0.05) enhanced the locomotor, motor, and exploratory activities namely total distance traveled, maximum speed, total time mobile, mobile episode, path efficiency, body rotation, absolute turn angle, and negative geotaxis when compared with rats exposed to MWCNTs alone. Further, kolaviron markedly abated the decrease in the acetylcholinesterase activity and antioxidant defense system as well as the increase in oxidative stress and inflammatory biomarkers induced by MWCNT exposure in the cerebrum, cerebellum, and mid-brain of rats. The amelioration of MWCNT-induced neuronal degeneration in the brain structures by kolaviron was verified by histological and morphometrical analyses. Taken together, kolaviron abated MWCNT-induced neurotoxicity via anti-inflammatory and redox regulatory mechanisms.