Modulation of the Nrf-2 and HO-1 signalling axis is associated with Betaine's abatement of fluoride-induced hepatorenal toxicities in rats.

Sodium fluoride (NaF) ingestion has several detrimental effects in humans and rodents. NaF mechanisms of toxicity include perturbation of intracellular redox homeostasis and apoptosis. Betaine (BET) is a modified amino acid with anti-inflammatory, antioxidant, and anti-apoptotic properties. This study investigates BET's effect on NaF-induced hepatorenal toxicities in rats. Experimental rats (n = 30) were randomly assigned to groups (n = 6) and treated by gavage for 28 days. Group I (2 mL of distilled water), Group II (NaF: 9 mg/kg) alone, Group III: (BET: 100 mg/kg), Group IV: (NaF: 9 mg/kg and BET 1: 50 mg/kg), and Group V: (NaF: 9 mg/kg and BET 2: 100 mg/kg). Our findings revealed significantly (p < 0.05) increased hepatic transaminase activities alongside creatinine and urea levels following NaF-alone treatment in addition to increased oxidative status, lipid peroxidation, reactive oxygen and nitrogen species, decreased superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase, glutathione, and total sulfhydryl groups. The reduced levels of nuclear factor erythroid 2-related factor-2 and the activities of heme oxygenase-1, thioredoxin, and thioredoxin reductase in NaF-alone treated rats equally compromised cellular molecular responses to oxidative stress. Also, NaF increased (p < 0.05) hepatorenal inflammatory biomarkers-nitric oxide, interleukin-10, myeloperoxidase, and xanthine oxidase. Furthermore, caspase-3 and caspase-9 were increased (p < 0.05) in rats treated with NaF alone. Contrastingly, BET was observed to alleviate the harmful effects of NaF. Treatment with BET mitigated NaF-induced oxido-inflammatory responses and apoptosis in the experimental rat's hepatorenal system. The study demonstrates the potential of BET to abate NaF-induced hepatorenal toxicity.

US air pollution is associated with increased incidence of non-syndromic cleft lip/palate.

Maternal cigarette use is associated with the fetal development of orofacial clefts. Air pollution should be investigated for similar causation. We hypothesize that the incidence of non-syndromic cleft lip with or without palate (NSCLP) and non-syndromic cleft palate (NSCP) would be positively correlated with air pollution concentration. METHODS: The incidence of NSCLP and NSCP per 1000 live births from 2016 to 2020 was extracted from the Centers for Disease Control and Prevention Vital Statistics Database and merged with national reports on air pollution using the Environmental Protection Agency Air Quality Systems annual data. The most commonly reported pollutants were analyzed including benzene, sulfur dioxide (SO2), particulate matter (PM) 2.5, PM 10, ozone (O3), and carbon monoxide (CO). Multivariable negative binomial and Poisson log-linear regression models evaluated the incidence of NSCLP and NSCP as a function of the pollutants, adjusting for race. All p-values are reported with Bonferroni correction. RESULTS: The median NSCLP incidence was 0.22/1000 births, and isolated NSCP incidence was 0.18/1000 births. For NSCLP, SO2 had a coefficient estimate (CE) of 0.60 (95% CI [0.23, 0.98], p < 0.007) and PM 2.5 had a CE of 0.20 (95% CI [0.10, 0.31], p < 0.005). Among isolated NSCP, no pollutants were found to be significantly associated. CONCLUSION: SO2 and PM 2.5 were significantly correlated with increased incidence of NSCLP. The American people and perinatal practitioners should be aware of the connection to allow for risk reduction and in utero screening.

Aflatoxin B1-induced dysfunction in male rats' reproductive indices were abated by Sorghum bicolor (L.Moench) hydrophobic fraction.

The burden of infertility distresses millions of families worldwide. The harmful effects of aflatoxin B1 (AFB1) on the reproductive system involve oxidative stress, culminating in inflammation and cellular apoptosis. The phytochemical in Sorghum bicolor is rich in antioxidants and anti-inflammatory activities. The effect of Sorghum bicolor (L.) Moench (SBE-HP) extract -hydrophobic fraction- enriched in Apigenin (API) was investigated in rats chronically dosed with AFB1 and the likely mechanism (s) of SBE-HP to protect against AFB1-induced reproductive toxicity. Adult Wistar male rats (twenty-four) were selected randomly and allocated into four groups. Cohort 1 was administered 0.05 % carboxymethyl cellulose (CMC); cohort 2 received AFB1 (50 µg/kg) alone; while cohorts 3 and 4 received 5 & 10 mg/kg of (SBE-HP) respectively, along with 50 µg/kg of AFB1. After 28 days, AFB1 induced remarkable reproductive toxicity as evidenced by increased sperm abnormalities, lowered sperm quality and motility, altered serum hormonal levels and testicular enzyme activities, decreased anti-oxidants, increased pro-oxidants, apoptotic and inflammatory biomarkers, as well as altered histoarchitectural structure of the testis, epididymis, and hypothalamus of rats. API-enriched extract of S. bicolor reduced AFB1-induced oxidative, inflammatory, apoptotic, and histological derangement by improving sperm function parameters, testicular enzymes, and reproductive hormones. Anti-oxidant levels and anti-inflammatory mediators were increased while decreases in the activities and levels of pro-oxidants, pro-inflammatory molecules and caspase-9 occurred in the rats' testes, epididymis, and hypothalamus. API-enriched S. bicolor protected the testes, epididymis, and hypothalamus of male rats exposed to AFB1 by modulating oxidative stress, inflammation, and apoptosis.

Co-exposure to aflatoxin B1 and therapeutic coartem worsens hepatic and renal function through enhanced oxido-inflammatory responses and apoptosis in rats.

Aflatoxin B1 (AFB1) is a mycotoxin synthesised as a secondary metabolite by members of the Aspergillus species contaminating agricultural produce. Aspergillus species thrive in tropical climes, endemic to malaria. Artemisinin-based combination therapies (ACTs) effectively treat and prevent malaria recrudescence; Coartem (COA) is an ACT whose toxicity is evident. Although there are scanty studies on COA toxicity, the scientific literature is replete on AFB1 toxic effects -including carcinogenicity. The current research investigates AFB1 and COA toxicity in experimental Wistar rats' hepatorenal systems. Thirty albino rats were randomly grouped into five cohorts (n = 6) and treated as follows: Group I: Untreated control (2 mL/kg of corn oil); group II: AFB1 alone (70 µg/kg); group III: COA alone (5 mg/kg); group IV: COA and a low dose of AFB11 (5 mg/kg & 35 µg/kg); while Group V: COA and a high dose AFB12 (5 mg/kg & 70 µg/kg) by gavage. Our results show that exposure to AFB1 and COA significantly (p < 0.05) reduced superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities, besides reduced glutathione and total sulfhydryl groups level. Reactive oxygen and nitrogen species, lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, nitric oxide, xanthine oxidase, and myeloperoxidase levels were increased (p < 0.05) in rats co-treated with COA and AFB1. Cell death was aggravated in COA and AFB1 groups, exemplified by increased Caspase-3 and 9 activities and alterations in the typical histological features of experimental rats' livers and kidneys. Finally, rats co-treated with AFB1 and COA experienced increased hepatorenal dysregulation, oxidative and inflammatory tissue damage, and apoptotic cell death. All the observed systemic perturbations occurred dose-dependently. It is crucial, therefore, to prevent AFB1 dietary contaminations during COA therapeutic regimen due to increased pathophysiological damage exerted on experimental rat liver and kidneys, as evidenced in this study.

The protective effect of 3-indolepropanoic acid on aflatoxin B1-induced systemic perturbation of the liver and kidney function in rats.

Aflatoxin B1 (AFB1) is known to derange the hepatorenal system by redox, DNA adduct formation and apoptotic networks. Endogenous 3-indole propionic acid (3-IPA) is a metabolite of tryptophan metabolism by gut microbiota that can protect against redox imbalance, inflammation and cellular lipid damage. We investigated the beneficial effect of 3-IPA against AFB1-mediated organ toxicity in male rats post 28 days of consecutive treatment. The 3-IPA (25 and 50 mg/kg) was orally administered alongside AFB1 (50 µg/kg) treatment. Biochemical and enzyme-linked immunosorbent assays were utilised to examine biomarkers of hepatorenal function, oxidative status and inflammation. DNA damage and apoptosis were also assessed, and histological staining techniques were used to investigate hepatorenal tissues for pathological indicators. The 3-IPA supplementation abated AFB1-mediated increases in biomarkers of hepatic and renal dysfunction in rat serum. Co-administration of 3-IPA further reduced AFB1-induced redox imbalance (by upregulating antioxidant mediators and enzymes [GSH, TSH, Trx, Trx-R, SOD, CAT, GPx and GST]; reducing reactive oxygen species, lipid peroxidation and DNA adduct [RONS, LPO and 8-OH-dG] formation; suppressing pro-inflammatory and apoptotic mediators [XO, MPO, NO, IL-1ß and Casp -9 and -3]; and upregulating the level of interleukin 10 (IL-10). Moreover, treatment with 3-IPA lessened hepatorenal tissue injuries. These findings suggest that augmenting 3-IPA endogenously from tryptophan metabolism may provide a novel strategy to forestall xenobiotics-mediated hepatorenal toxicity, including AFB1.

A biochemical and histology experimental approach to investigate the adverse effect of chronic lead acetate and dietary furan on rat lungs.

Despite lead widespread environmental pollution, its effect on humans and livestock's respiratory systems remains inadequately investigated. Similarly, furan is industrially relevant with enormous environmental presence. Lead and furan can be ingested -via lead pipes contaminated water and heat-treated food respectively. Thus, humans are inadvertently exposed continuously. Lead toxicity is well studied, and furan have earned a position on the IARC's list of carcinogens. Here, we evaluate the effect of co-exposure to lead and furan on rat lungs. Thirty Wistar rats were grouped randomly into six cohorts (n = 6) consisting of a control group, furan alone group, lead acetate (PbAc) alone group and three other groups co-exposure to graded PbAc (1, 10 & 100 µg/L) alongside a constant furan (8 mg/kg) dose. After twenty-eight days, enzymatic and non-enzymatic antioxidant, oxidative stress and inflammatory biomarkers were biochemically evaluated. The ELISA-based technique was used to measure oxidative-DNA damage (8-OHG), tumour protein 53 (TP53) expressed and tumour necrotic factor-alpha (TNF-α) level. Dose-dependent increases (p < 0.05) in reactive oxygen and nitrogen species, malondialdehyde, nitric oxide, myeloperoxidase, TNF-α and TP53 level, with an associated decrease (p < 0.05) in enzymatic and non-enzymatic antioxidants were observed in the furan, PbAc and the co-treated rats relative to the control. In addition, PbAc and furan treatment impaired the histoarchitectural structures of rat lungs, exemplified by pro-inflammatory cell infiltration and trafficking into the bronchioles and alveolar spaces. Co-exposure to furan and PbAc may contribute to lung dysfunction via loss of redox balance, genomic damage/instability, inflammation and disrupted histoarchitectural features.

Exposure to lead and dietary furan intake aggravates hypothalamus-pituitary-testicular axis toxicity in chronic experimental rats.

Lead (Pb) and furan are toxic agents, and persistent exposure may impair human and animal reproductive function. We therefore explored the effects of Pb and furan on male rat hypothalamic-pituitary-gonadal reproductive status, oxidative stress, inflammation, and genomic integrity. We found that co-exposure to Pb and furan reduced the activities of testicular function enzymes, endogenous antioxidant levels, total sulfhydryl group, and glutathione. Sperm abnormality, biomarkers of oxidative stress, inflammation, and p53 expression were increased in a dose-dependent manner by treatment with furan and Pb. Typical rat gonad histoarchitecture features were also damaged. Conclusively, co-exposure to Pb and furan induced male reproductive function derangement by decreasing the antioxidant defences in rats, increasing abnormalities in spermatozoa morphology, and reducing reproductive hormone in circulation. These pathophysiological alterations, if persistent, might provide a permissive environment for potentiating reproductive dysfunction and infertility.

Accidental lead in contaminated pipe-borne water and dietary furan intake perturbs rats' hepatorenal function altering oxidative, inflammatory, and apoptotic balance.

Inadvertent exposure to furan and Pb is associated with hepatorenal abnormalities in humans and animals. It is perceived that these two chemical species may work in synergy to orchestrate liver and kidney damage. Against this background, we investigated the combined effect of furan and incremental lead (Pb) exposure on hepatorenal dysfunction. Wistar rats (n = 30; 150 g) were treated for 28 days accordingly: Control; FUR (8 mg/kg), PbAc (100 µg/L), FUR + PbAc1 (8 mg/kg FUR + 1 µg/L PbAc); FUR + PbAc1 (8 mg/kg FUR + 10 µg/L PbAc), and FUR + PbAc1 (8 mg/kg FUR + 100 µg/L PbAc). Biomarkers of hepatorenal function, oxidative stress, inflammation, DNA damage, and apoptosis were examined. Furan and incrementally Pb exposure increased the levels of hepatorenal biomarkers and oxidative and pro-inflammatory mediators, including lipid peroxidation, reactive oxygen and nitrogen species, and interleukin-1 beta. Increased DNA damage, caspases- 9 and -3, and atypical histoarchitecture of the hepatorenal tissues exemplified furan and Pb treatment-related perturbations. Furthermore, the levels of antioxidants and IL-10 were also suppressed. Furan and Pb dose-dependently exacerbated hepatorenal derangements by altering the redox and inflammatory rheostats, worsened DNA damage, and related apoptotic onset that may potentiate hepatorenal disorders in humans and animals. The findings validate the synergistic effect of furan and Pb in the pathophysiology of kidney and liver disorders.

Apigeninidin-enriched Sorghum bicolor (L. Moench) extracts alleviate Aflatoxin B1-induced dysregulation of male rat hypothalamic-reproductive axis.

We examined the protective effect of the apigeninidin (API)-enriched fraction from Sorghum bicolor sheaths extracts (SBE-05, SBE-06, and SBE-07) against aflatoxin B1 (AFB1)-induced dysregulation of male rat's reproductive system that may trigger infertility. Male rats (160 ± 12 g) were treated with AFB1 (50 µg/kg) along with 5 or 10 mg/kg of SBE-05, SBE-06, and SBE-07 for 28 days. Subsequently, we assessed the reproductive hormone-prolactin, FSH, LH, testosterone levels, and testicular function enzymes. Moreover, we examined rats' testes, epididymis, and hypothalamus for oxidative and inflammatory stress biomarkers, caspase-9 activity and tissues pathology. We observed that comparative to AFB1 alone treated rats, API co-treatment significantly (p < 0.05) abated the AFB1-mediated decrease in prolactin and antioxidant defenses and lessened lipid peroxidation (LPO) and reactive oxygen and nitrogen species levels in the examined organs-testes, epididymis, and hypothalamus. API abated AFB1-induced hormone decreases-testosterone, FSH, and LH; and caused improvement in sperm quantity and quality. API lessened AFB1-mediated increase in pro-inflammatory cytokine, increased interleukin-10 level, an anti-inflammatory cytokine and reduced caspase-9 activities. In addition, API reduced alterations in the examined tissue histology. Our findings suggest that S. bicolor API-enrich extracts have active antioxidative, antiapoptotic, and anti-inflammatory activities, which can protect against AFB1-induced dysfunction of the hypothalamic-pituitary-gonadal axis.

Indigenous Nigeria medicinal herbal remedies: A potential source for therapeutic against rheumatoid arthritis.

Rheumatoid arthritis (RA) is a debilitating disease associated with locomotion impairment, and conventional therapeutic drugs are not optimal for managing RA. There is an avalanche of medications used for the management of RA. Still, studies have shown that they are associated with severe side effects, including hepatotoxicity, retinopathy, and cardiotoxicity disorders of the central nervous system (CNS), skin, blood, and infections. Complementary and alternative medicine (CAM) is currently gaining attention as a novel panacea for managing debilitating diseases, such as RA. Nigerian folk herbal remedies are replete with a plethora of curative medicine, albeit unvalidated scientifically but with seemingly miraculous provenance. Studies of the identification of bioactive compounds present in these botanicals using advanced spectral analytical techniques have enhanced our understanding of the role of Nigerian herbal remedies in the treatment and management of RA. Interestingly, experimental studies abound that the bioactive compounds present in the extracts of plant botanicals protected animals from the development of RA in different experimental models and reduced the toxicity associated with conventional therapeutics. Validated mechanisms of RA amelioration in human and animal models include suppression of the expression of NF-κB, IL-1ß, TNF-α, IL-6, IL-8, IL-17, IL-23, chemokines, TGF-ß, RANKL, RANK, iNOS, arginase, COX-2, VEGFA, VEGFR, NFATC1, and TRAP in the synoviocytes. Decreased ROS, NO, MDA, carbonyl groups, and PGE2 in the synovial fluid increased the expression of PPARα/γ; antioxidant and anti-inflammatory molecules also improve RA etiology. In this mini-review, we discuss the global burden of RA, the novel role of plant-based botanicals as potential therapeutics against signaling pathways in RA. Also addressed is the possible repurposing/reprofiling of plant botanicals to increase their therapeutic index among RA patients that patronize traditional healers in Nigeria with a global projection.

Apigeninidin-rich Sorghum bicolor (L. Moench) extracts suppress A549 cells proliferation and ameliorate toxicity of aflatoxin B1-mediated liver and kidney derangement in rats.

Sorghum bicolor plant has a high abundance of 3-deoxyanthocyanins, flavonoids and other polyphenol compounds that have been shown to offer numerous health benefits. Epidemiological studies have linked increased intake of S. bicolor to reduced risk of certain cancer types, including lung adenocarcinoma. S. bicolor extracts have shown beneficial effects in managing hepatorenal injuries. This study investigated the cytotoxic potential of three apigeninidin-rich extracts of S. bicolor (SBE-05, SBE-06 and SBE-07) against selected cancer cell lines and their ameliorative effect on aflatoxin B1 (AFB1)-mediated hepatorenal derangements in rats. We observed that, among the three potent extracts, SBE-06 more potently and selectively suppressed the growth of lung adenocarcinoma cell line (A549) (IC50 = 6.5 µg/mL). SBE-06 suppressed the expression of STAT3 but increased the expression of caspase 3. In addition, SBE-05, SBE-06 and SBE-07 inhibited oxidative and nitrosative stress, inflammation, and apoptosis and preserved the histoarchitectural networks of the liver and kidney of rats treated with AFB1. These in vitro and in vivo studies indicate the potential of these cheap and readily accessible extracts for cancer therapy and as chemo-preventive agents in preventing aflatoxin-related health issues.

Caffeic acid mitigates aflatoxin B1-mediated toxicity in the male rat reproductive system by modulating inflammatory and apoptotic responses, testicular function, and the redox-regulatory systems.

Aflatoxin B1 (AFB1 ) is a toxic metabolite of public health concern. The present study investigates the protective effects of caffeic acid (CA) against AFB1 -induced oxidative stress, inflammation, and apoptosis in the hypothalamus, epididymis, and testis of male rats. Five experimental rat cohorts (n = 6) were treated per os for 28 consecutive days as follows: Control (Corn oil 2 ml/kg body weight), AFB1 alone (50µg/kg), CA alone (40 mg/kg) and the co-treated rat cohorts (AFB1 : 50µg/kg + CA1: 20 or 40 mg/kg). Following sacrifice, the biomarkers of hypothalamic, epididymal, and testicular toxicities, antioxidant enzyme activities, myeloperoxidase (MPO) activity, as well as levels of nitric oxide (NO), reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO) were analysed spectrophotometrically. Besides, the concentration of tumour necrosis factor-alpha (TNF-α), Bcl-2 and Bax proteins were assessed using ELISA. Results showed that the AFB1 -induced decrease in biomarkers of testicular, epididymal and hypothalamic toxicity was significantly (p < .05) alleviated in rats coexposed to CA. Moreover, the reduction of antioxidant status and the increase in RONS and LPO were lessened (p < .05) in rats co-treated with CA. AFB1 mediated increase in TNF-α, Bax, NO and MPO activity were reduced (p< .05) in the hypothalamus, epididymis, and testis of rats coexposed to CA. In addition, Bcl-2 levels were reduced in rats treated with CA dose-dependently. Light microscopic examination showed that histopathological lesions severity induced by AFB1 were alleviated in rats coexposed to CA. Taken together, the amelioration of AFB1 -induced neuronal and reproductive toxicities by CA involves anti-inflammatory, antioxidant, antiapoptotic mechanisms in rats. PRACTICAL APPLICATIONS: The beneficial antioxidant effects of caffeic acid (CA) are attributed to CA delocalized aromatic rings and free electrons, easily donated to stabilize reactive oxygen species. We report in vivo findings on CA and AfB1 mediated oxidative stress and reproductive dysfunction in rats. CA conjugated esters including chlorogenic acids are widely distributed in plants, and they act as a dietary source of natural defense against infections. CA can chelate heavy metals and reduce production of damaging free radicals to cellular macromolecules. Along these lines, CA can stabilize aflatoxin B1-epoxide as well and avert deleterious conjugates from forming with deoxyribonucleic acids. Hence CA, as a dietary phytochemical can protect against the damaging effects of toxins including aflatoxin B1 that contaminate food. CA dose-dependently abated oxidative, inflammatory, and apoptotic stimuli, improved functional characteristics of spermatozoa and reproductive hormone levels, and prevented histological alterations in experimental rats' hypothalamus and reproductive organs brought about by AFB1 toxicity.

Caffeic acid protects against DNA damage, oxidative and inflammatory mediated toxicities, and upregulated caspases activation in the hepatorenal system of rats treated with aflatoxin B1.

Aflatoxicosis can induce largescale toxicities in predisposed populations. Food fortification with adequate antioxidant sources may reduce the toxic burden from aflatoxicosis. We examined the individual and combined effect of Caffeic acid (CA) on the aflatoxin B1 (AFB1)-induced hepatic and renal injury in male rats. Five experimental rat cohort (n = 6) consisting of the control (2 mL/kg corn oil), AFB1 alone (50 µg/kg), CA alone (40 mg/kg), AFB1+CA1 (50 µg/kg + 20 mg/kg) and AFB1+CA2 (50 µg/kg + 40 mg/kg) were so treated for 28 consecutive days. Upon sacrifices, diagnostic markers of hepatorenal functions, oxidative stress, inflammation, oxidative deoxyribonucleic acid -DNA-damage and apoptosis were analysed. Our results showed that CA reduced AFB1-induced toxicities in rats' liver and kidneys by significantly increasing (p < 0.05) endogenous antioxidant and the anti-inflammatory IL-10 level. Caffeic acid simultaneously reduced hepatic and renal dysfunction biomarkers in the serum, oxidative stress, and lipid peroxidation levels. Besides, CA diminished reactive oxygen and nitrogen species, inflammatory nitric oxide levels, interleukin-1 ß and the activities of xanthine oxidase and myeloperoxidase. Additionally, CA reduced DNA damage and caspase-mediated apoptotic responses and preserved the cytoarchitecture of rats' liver and kidneys treated with AFB1. These data suggest that CA can be used as a food additive to mitigate AFB1-induced toxicity in the examined organs.

Protocatechuic acid protects against hepatorenal toxicities in rats exposed to Furan.

Furan formed in processed food is hepatotoxic and likely carcinogenic in humans. We investigated protocatechuic acid (PCA) protective role in rats' hepatorenal function treated with furan. Rats were grouped and treated as follows: Control, PCA (50 mg/kg), furan alone (8 mg/kg), furan + PCA1 (25 + 8 mg/kg), and furan + PCA2 (50 + 8 mg/kg). Upon sacrifice, evaluation of hepatorenal function, oxidative stress status, reactive oxygen and nitrogen species (RONS), lipid peroxidation (LPO), myeloperoxidase (MPO) activity, among nitric oxide (NO) levels were performed. Cytokine levels (IL-10, IL-1ß, TNF-alpha), Caspase 3 and 9 activities, and histopathological examination were also assessed. We found that the final body and relative liver weights changed significantly (p < 0.05) in treated groups. Hepatic transaminases, urea, and creatinine increased (p < 0.05) in furan only treated group, and reduced in PCA co-treated groups. The furan-induced decrease in antioxidant status increased RONS, and LPO levels were alleviated (p < 0.05) by PCA co-treatment. Furthermore, furan-mediated increase in NO, IL-1ß, TNF-alpha levels, MPO, Cas-3, and 9 activities and suppressed IL-10 levels was reversed accordingly in rats' kidney and liver co-treated with PCA. The extent of furan-mediated hepatorenal lesions was lessened in PCA co-treated rats. Our findings suggest that PCA protects against oxido-inflammatory pathways, enhanced caspases 3 and 9 activations induced by furan in rat hepatorenal system.

Biochemical and histological alterations of doxorubicin-induced neurotoxicity in rats: Protective role of luteolin.

Doxorubicin (DOX) is a chemotherapeutic drug used in the treatment of various cancer types. DOX toxic side effects include neuronopathy and memory deficits. We investigated the effect of the antioxidant luteolin (LUT: 50 or 100 mg/kg; per os) on DOX (2 mg/kg; intraperitoneal)-induced oxidative stress (OS), inflammation, and apoptosis in the brain of Wistar rats for 14 days. We observed that LUT reduced DOX-mediated increase in OS biomarkers-catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase. LUT increased glutathione and total sulphydryl levels and alleviated DOX-induced increases in the levels of reactive oxygen and nitrogen species, lipid peroxidation, myeloperoxidase, nitric oxide, tumor necrosis factor-α, and interleukin-1ß (IL-1ß). Additionally, LUT suppressed caspase-3 activity, increased anti-inflammatory cytokine-IL-10 level, and reduced pathological lesions in the examined organs of rats cotreated with LUT and DOX. Collectively, cotreatment with LUT lessened DOX-induced neurotoxicity. Supplementation of LUT as a chemopreventive agent might be useful in patients undergoing DOX chemotherapy.

3-Indolepropionic acid upturned male reproductive function by reducing oxido-inflammatory responses and apoptosis along the hypothalamic-pituitary-gonadal axis of adult rats exposed to chlorpyrifos.

We examined the effect of 3-Indolepropionic acid (3-IPA), an antioxidant on the organophosphorus pesticide chlorpyrifos (CPF)-induced reproductive toxicity in rats. The five experimental rat cohorts were treated per os for 14 consecutive days as follows: Control (Corn oil 2 mL/kg body weight), CPF alone (5 mg/kg), 3-IPA alone (40 mg/kg) and the co-treated rat cohorts (CPF:5 mg/kg + 3-IPA: 20 or 40 mg/kg). Biomarkers of testicular and epididymal function, oxidative stress, myeloperoxidase (MPO) activity and the levels of nitric oxide (NO), reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO) were assessed. Also, tumour necrosis factor-alpha (TNF-α), Bcl-2-associated X (Bax) and B cell lymphoma 2 (Bcl-2) proteins were estimated, and tissue histology was microscopically examined. CPF alone significantly (p < 0.05) increased biomarkers of reproductive toxicities were averted in rats co-treated 3-IPA. Decreases in antioxidants and increases in lipid peroxidation and reactive oxygen and nitrogen species were lessened (p < 0.05) in CPF and 3-IPA co-treated rats. CPF mediated increases in TNF-α, NO, Bax, and MPO activity was reduced (p < 0.05) in the epididymis, testes, and hypothalamus of rats co-treated with 3-IPA. In addition, Bcl-2 expression was increased in rats co-treated with 3-IPA dose-dependently. Histopathological examination revealed severe lesions induced by CPF were prevented in rats co-treated with 3-IPA. Our findings demonstrate that exogenous 3-IPA reduced CPF-induced oxidative stress, inflammation, and apoptosis in the epididymis and testes of male rats.

Combine effect of exposure to petrol, kerosene and diesel fumes: On hepatic oxidative stress and haematological function in rats.

Petroleum product fumes (PPFs) containing toxic organic components are pervasive in the environment, emanating from anthropogenic activities, including petroleum exploration and utilization by end-user activities from petrol-gasoline stations. Petrol station attendants are exposed to PPF through inhalation and dermal contact with consequent toxicological implications. We investigated the effects of chronic exposure (60 and 90 days) to petrol (P), kerosene (K) and diesel (D) alone and combined exposure to petrol, kerosene and diesel (PKD) fumes on hepatotoxicity, haematological function and oxidative stress in rats. Following sacrifice, we evaluated hepatic damage biomarkers, blood glucose, oxidative stress and haematological function. Chronic exposure to PPF significantly increased organo-somatic indices, blood glucose, biomarkers of hepatic toxicity and oxidative stress in an exposure duration-dependent manner. There was a simultaneous decrease in the protective capacity of antioxidants. Furthermore, exposure to PPF increased pro-inflammatory biomarkers in rats (90 > 60 days). Regardless of exposure duration, plateletcrit, mean platelet volume, platelet distribution width and red cell distribution width in the coefficient of variation increased, whereas red blood cell count, haemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, white blood cell, lymphocyte, monocyte-basophil-eosinophil mixed counts and platelet count decreased after 60 and 90 days exposure. Microscopic examination of the liver demonstrated hepatic pathological changes paralleling the duration of exposure to PKD fumes. However, the injury observed was lesser to that of rats treated with the diethylnitrosamine - positive control. Our results expanded previous findings and further demonstrated the probable adverse effect on populations' health occasioned by persistent exposure to PPF. Individuals chronically exposed by occupation to PPF may be at greater risk of developing disorders promoted by continuous oxido-inflammatory perturbation and suboptimal haematological-immunologic function - thereby enabling a permissive environment for pathogenesis notwithstanding the limitation of quantifying PPF absolute values in our model system.

Chlorogenic acid co-administration abates tamoxifen-mediated reproductive toxicities in male rats: An experimental approach.

Reports over the years have demonstrated toxic side effect-including reproductive toxicity- of tamoxifen (TAM), a drug of choice in the management of primary breast cancer. Chlorogenic acid (CGA), a dietary polyphenol, reportedly elicits beneficial pharmacological effects. However, the impact of CGA on TAM-associated reproductive toxicity is absent in the literature. We, therefore, experimented on CGA's effect and TAM-mediated reproductive toxicity in rats. Cohorts of rats were treated with TAM (50 mg/kg) or co-treated with CGA (25 or 50 mg/kg) for 14 consecutive days. The result showed that treatment of CGA significantly increases testosterone, LH, and FSH levels compared to the TAM group. However, prolactin level was markedly decreased after pretreatment of CGA in TAM-treated rats. CGA abated TAM-induced decreases acid phosphatase, alkaline phosphatase, and antioxidant enzymes in the testis. CGA alleviated TAM-facilitated surges of reactive oxygen and nitrogen species, myeloperoxidase, nitric oxide, interleukin-1ß, and tumor necrosis factor-alpha in rats epididymis and testes. Additionally, CGA increased anti-inflammatory cytokine -interleukin-10-, suppressed caspase-3 activity, and reduced pathological lesions in the examined organs of rats co-treated with CGA and TAM. CGA phytoprotective effect improved reproductive function occasioned by TAM-mediated toxicities in rats, by abating oxido-inflammatory damages and downregulating apoptotic responses. PRACTICAL APPLICATIONS: CGA protects against the damaging oxido-inflammatory responses incumbent on TAM metabolism. As an antioxidant abundant in plant-derived foods, CGA reportedly protects against inflammatory damage, hypertension, and neurodegenerative diseases. We present evidence that CGA ameliorates TAM-induced reproductive dysfunction by suppressing oxidative and inflammation stress downregulate apoptosis and improve reproductive function biomarker in rats.

Co-administration of Luteolin mitigated toxicity in rats' lungs associated with doxorubicin treatment.

Doxorubicin (DOX), is a drug against lung malignancies with undesirable side effect including oxidative, inflammatory and apoptotic effects. Luteolin (LUT), present in fruits and vegetables is pharmacologically active against oxido-inflammatory and apoptotic responses. The present study examined the effect of LUT on DOX-induced lungs and blood dysfunction in Wistars rat (sex: male; 10 weeks old, 160 ± 5 g). Randomly grouped (n = 10) rats were treated as follows: control, LUT alone (100 mg/kg; per os), DOX (2 mg/kg; i. p), and co-treated rats with LUT (50 or 100 mg/kg) and DOX for two consecutive weeks. DOX alone adversely altered the final body and relative organ weights, red and white blood cell and platelet counts. DOX significantly (p > 0.05) reduced lungs antioxidant capacity, and anti-inflammatory cytokines; increased biomarkers of oxidative stress, caspase-3 activity, and pro-inflammatory cytokine. Morphological damages accompanied these biochemical alterations in the lung of experimental rats. Co-treatment with LUT, dose-dependently reversed DOX-mediated changes in rats' survival, toxic responses, and diminished oxidative stress in rat's lungs. Furthermore, co-treatment with LUT resulted in the reduction of pro-inflammatory cytokines and apoptotic biomarkers, increased red and white blood cell, platelet counts and abated pathological injuries in rat lungs treated with DOX alone. In essence, our findings indicate that LUT dose-dependently mitigated DOX-induced toxicities in the lungs and haematopoietic systems. Supplementation of patients on DOX-chemotherapy with phytochemicals exhibiting antioxidant activities, specifically LUT, could circumvent the onset of unintended toxic responses in the lungs and haematopoietic system exposed to DOX.

Factors Associated with Exclusive Breastfeeding Practice among Nursing Mothers in rural areas of Enugu State and its Implications for Social Work Practice in Nigeria.

This study investigates factors that influence exclusive breastfeeding practice. Focus group discussions involving 60 nursing mothers from selected rural areas of Enugu State, Nigeria, was adopted. Thematic analysis was adopted in analyzing data collected. Findings show that nursing mothers in the study area are yet to fully accept the 6 months' practice of exclusive breastfeeding. Issues relating to culture, economic hardship, and support networks were revealed to exercise gross influence on practice of exclusive breastfeeding. The study concluded that professional support from social workers is very vital to achieving conformity to the practice. This can be done through awareness creation that would accommodate support networks, while adopting exclusive breastfeeding campaign models that have proven successful in other African nations.