Epirubicin Treatment Induces Neurobehavioral, Oxido-Inflammatory and Neurohistology Alterations in Rats: Protective Effect of the Endogenous Metabolite of Tryptophan - 3-Indolepropionic Acid.

Epirubicin's (EPI) efficacy as a chemotherapeutic agent against breast cancer is limited by EPI's neurotoxicity associated with increased oxidative and inflammatory stressors. 3-Indolepropionic acid (3-IPA) derived from in vivo metabolism of tryptophan is reported to possess antioxidative properties devoid of pro-oxidant activity. In this regard, we investigated the effect of 3-IPA on EPI-mediated neurotoxicity in forty female rats (180-200 g; five cohorts (n = 6) treated as follows: Untreated control; EPI alone (2.5 mg/Kg); 3-IPA alone (40 mg/Kg body weight); EPI (2.5 mg/Kg) + 3-IPA (20 mg/Kg) and EPI (2.5 mg/Kg) + 3-IPA (40 mg/Kg) for 28 days. Experimental rats were treated with EPI via intraperitoneal injection thrice weekly or co-treated with 3-IPA daily by gavage. Subsequently, the rat's locomotor activities were measured as endpoints of neurobehavioural status. After sacrifice, inflammation, oxidative stress and DNA damage biomarkers were assessed in rats' cerebrum and cerebellum alongside histopathology. Our results demonstrated that locomotor and exploratory deficits were pronounced in EPI-alone treated rats and improved in the presence of 3-IPA co-treatment. EPI-mediated decreases in tissue antioxidant status, increases in reactive oxygen and nitrogen species (RONS), as well as in lipid peroxidation (LPO) and xanthine oxidase (XO) were lessened in the cerebrum and cerebellum of 3-IPA co-treated rats. Increases in nitric oxide (NO) and 8-hydroxydeguanosin (8-OHdG) levels and myeloperoxidase MPO activity were also abated by 3-IPA. Light microscopic examination of the cerebrum and cerebellum revealed EPI-precipitated histopathological lesions were subsequently alleviated in rats co-treated with 3-IPA. Our findings demonstrate that supplementing endogenously derived 3-IPA from tryptophan metabolism enhances tissue antioxidant status, protects against EPI-mediated neuronal toxicity, and improves neurobehavioural and cognitive levels in experimental rats. These findings may benefit breast cancer patients undergoing Epirubicin chemotherapy.

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.

The Hydrophobic Extract of Sorghum bicolor (L. Moench) Enriched in Apigenin-Protected Rats against Aflatoxin B1-Associated Hepatorenal Derangement.

Aflatoxin B1 (AFB1) is a recalcitrant metabolite produced by fungi species, and due to its intoxications in animals and humans, it has been classified as a Group 1 carcinogen in humans. Preserving food products with Sorghum bicolor sheath can minimise the contamination of agricultural products and avert ill health occasioned by exposure to AFB1. The current study investigated the ameliorating effect of Sorghum bicolor sheath hydrophobic extract (SBE-HP) enriched in Apigenin (API) on the hepatorenal tissues of rats exposed to AFB1. The SBE-HP was characterised using TLC and LC-MS and was found to be enriched in Apigenin and its methylated analogues. The study used adult male rats divided into four experimental cohorts co-treated with AFB1 (50 µg/kg) and SBE-HP (5 and 10 mg/kg) for 28 days. Biochemical, enzyme-linked immunosorbent assays (ELISA) and histological staining were used to examine biomarkers of hepatorenal function, oxidative status, inflammation and apoptosis, and hepatorenal tissue histo-architectural alterations. Data were analysed using GraphPad Prism 8.3.0, an independent t-test, and a one-way analysis of variance. Co-treatment with SBE-HP ameliorated an upsurge in the biomarkers of hepatorenal functionality in the sera of rats, reduced the alterations in redox balance, resolved inflammation, inhibited apoptosis, and preserved the histological features of the liver and kidney of rats exposed to AFB1. SBE-HP-containing API is an excellent antioxidant regiment. It can amply prevent the induction of oxidative stress, inflammation, and apoptosis in the hepatorenal system of rats. Therefore, supplementing animal feeds and human foods with SBE-HP enriched in Apigenin may reduce the burden of AFB1 intoxication in developing countries with a shortage of effective antifungal agents.

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.

Coadministration of gallic acid abates zearalenone-mediated defects in male rat's reproductive function.

As gallic acid (GA) role in zearalenone (ZEN); mediated reproductive dysfunction has not been studied, we report on GA's effect on reproductive dysfunction in rats treated with ZEN-100 µg/kg alone, or with GA-40 mg/kg; for 4 weeks. The mycotoxin ZEN contaminates crops, causing toxicity on ingestion, economic losses, and alters reproductive function. Relative to control, GA reversed ZEN-induced reduction of rats' testicular function enzymes and reproductive hormones and improved ZEN-impaired sperm quality. GA significantly (p < 0.05) increased rats antioxidant status, inhibited (p < 0.05) reactive oxygen and nitrogen species and lipid peroxidation levels, and abated (p < 0.05) proinflammatory biomarkers in the examined organs: hypothalamus, testis, and epididymis. Histopathology revealed that GA facilitated the preservation of testicular and epididymal cytoarchitecture significantly altered in rat cohorts treated with ZEN alone. Conclusively, GA protected against ZEN-induced toxicity in the rats' organs examined, enhanced endogenous antioxidative protective mechanism, and abated proinflammatory responses. GA further averted a decline in circulatory, reproductive enzymes, hormone levels. GA also protected against reproductive tissue damage and improved parameters of sperm functionality.

Chloroform extract of Calliandra portoricensis inhibits tumourigenic effect of N-methyl-N-nitrosourea and benzo(a)pyrene in breast experimental cancer.

Calliandra portoricensis (C. portoricensis) is used in herbal homes in Nigeria to manage breast diseases. We investigated the anti-tumourigenic effects of chloroform extract of C. portoricensis (CP) in breast experimental cancer induced by N-methyl-N-nitrosourea (NMU) and benzo-(a)-pyrene (BaP). Fifty-six female rats were assigned into seven equal groups: Group 1 served as control, group 2 received NMU and BaP (50 mg/kg, each), groups 3 and 4 received [NMU + BaP] and treated with CP at 50 and 100 mg/kg, respectively. Group 5 received CP (100 mg/kg), group 6 received [NMU + BaP] and vincristine (0.5 mg/kg), while group 7 received vincristine (0.5 mg/kg). The NMU and BaP (i.p) were dissolved in normal saline and corn oil, respectively. The CP (oral) and vincristine (i.p) were given thrice and twice per week, respectively for 10 weeks. The [NMU + BaP] intoxication significantly decreased body weight gain by 32% while organo-somatic weight of mammary gland increased by 37%. Also, [NMU + BaP] decreased the activities of mammary catalase, glutathione-s-transferase, glutathione peroxidase, superoxide dismutase and total sulphurhydryl by 34%, 31%, 35%, 35% and 33%, respectively. The [NMU + BaP] increased inflammatory and oxidative stress markers; nitrite, lipid peroxidation and myeloperoxidase by 62%, 57% and 361%, respectively. Strong expression of BCL-2, IL-6, COX 2, ß-catenin and iNOS in [NMU + BaP]-administered rats were observed. Histology revealed glands with malignant epithelial cells and high nucleocytoplasm in [NMU + BaP] rats. Treatment with CP attenuated inflammation, apoptosis and restored cyto-architecture of mammary gland. Overall, CP abates mammary tumourigenesis by targeting cellular pathways of inflammation and apoptosis.

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.

Ameliorative effects of hexane extract of Garcinia kola seeds Heckel (Clusiaceae) in cisplatin-induced hepatorenal toxicity in mice.

Garcinia kola seed is used to manage liver diseases in ethnomedicine. However, there is limited information on its role in Cisplatin (CIS)-induced toxicity. Here, we investigated the potential of hexane extract of Garcinia kola (HEGK) in lessening CIS-induced hepatorenal- and gene- toxicity. Male mice (22 ± 3 g) randomly assigned into groups (n = 5) were treated for five days: Corn oil only, HEGK (200 mg/kg), CIS (20 mg/kg; i.p; 48-hours), CIS + HEGK (100 mg/kg), CIS + HEGK (200 mg/kg), CIS + Quercetin (25 mg/kg), and Quercetin(25 mg/kg). Corn oil, HEGK, and Quercetin were administered daily by gavage. GC-MS revealed the presence of 9,19-Cyclolanost-24-en-3-ol as the most abundant component in HEGK, with an LC50 of 1023 µg/mL. HEGK significantly (p < 0.05) scavenged DPPH, inhibited lipid peroxidation and exhibited reducing activity dose-dependently. CIS treatment increased (p < 0.05) urinary albumin and creatinine by 18 and 56%, respectively, serum levels of total bilirubin, creatinine, and hepatic transaminases, while albumin decreased (p < 0.05) by 57%. CIS treatment increased renal and hepatic malondialdehyde (MDA) levels by 67 and 70% individually, while the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were decreased (p < 0.05). Furthermore CIS-induced the formation of mononucleated polychromatic erythrocytes (mnPCEs) 150% in the bone marrow of mice. Histology revealed necrosis of hepatocytes, congestion of renal interstitial vessel, and hyperplasia of the Kupffer cells. Pretreatment with HEGK reduced the levels of MDA, mnPCEs, and increased the activities of antioxidant enzymes and restored GSH to levels comparable in control mice. Taken together, HEGK ameliorated CIS-toxicity via the activation of the antioxidative pathways and mitigated genotoxicity by mitigating mnPCEs formation in mice.

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.

Neuroprotective role of gallic acid in aflatoxin B1 -induced behavioral abnormalities in rats.

The neurotoxic impact of dietary exposure to aflatoxin B1 (AFB1 ) is documented in experimental and epidemiological studies. Gallic acid (GA) is a triphenolic phytochemical with potent anticancer, anti-inflammatory, and antioxidant activities. There is a knowledge gap on the influence of GA on AFB1 -induced neurotoxicity. This study probed the influence of GA on neurobehavioral and biochemical abnormalities in rats orally treated with AFB1 per se (75 µg/kg body weight) or administered together with GA (20 and 40 mg/kg) for 28 uninterrupted days. Behavioral endpoints obtained with video-tracking software demonstrated significant (p < .05) abatement of AFB1 -induced 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 AFB1 and GA was confirmed by track plots and heat maps appraisal. Abatement of AFB1 -induced decreases in acetylcholinesterase activity, antioxidant status and glutathione level by GA was accompanied by a marked reduction in oxidative stress markers in the cerebellum and cerebrum of rats. Additionally, GA treatment abrogated AFB1 -mediated decrease in interleukin-10 and elevation of inflammatory indices, namely tumor necrosis factor-α, myeloperoxidase activity, interleukin-1ß, and nitric oxide. Further, GA treatment curtailed caspase-3 activation and histological injuries in the cerebral and cerebellar tissues. In conclusion, abatement of AFB1 -induced neurobehavioral abnormalities by GA involves anti-inflammatory, antioxidant, and antiapoptotic mechanisms in rats.

Rutin ameliorates copper sulfate-induced brain damage via antioxidative and anti-inflammatory activities in rats.

Excessive exposure to Copper (Cu) may result in Cu toxicity and adversely affect health outcomes. We investigated the protective role of rutin on Cu-induced brain damage. Experimental rats were treated as follows: group I: control; group II: Cu-sulfate: 200 mg/kg; group III: Cu-sulfate, and rutin 100 mg/kg; and group IV: rutin 100 mg/kg, for 7 weeks. Cu only treatment significantly decreased body weight gain, while rutin cotreatment reversed this decrease. Cu treatment increased malondialdehyde, nitric oxide level, and myeloperoxidase activity and decreased superoxide dismutase and catalase activities in rat brain. Immunohistochemistry showed that COX-2, iNOS, and Bcl-2 proteins were strongly expressed, while Bax was mildly expressed in the brain of Cu-treated rats. Furthermore, brain histology revealed degenerated neurons, and perforated laminae of cerebral cortex in the Cu-only treated rats. Interestingly, coadministration of Cu and rutin reduced the observed histological alteration, improved inflammatory and antioxidant biomarkers, thereby protecting against Cu-induced brain damage via antioxidative and anti-inflammatory mechanisms.

N-acetyl cysteine co-treatment abates perfluorooctanoic acid-induced reproductive toxicity in male rats.

Perfluorooctanoic acid is a synthetic perfluoroalkyl-persistent in the environment and toxic to humans. N-acetylcysteine is a pro-drug of both amino acid l-cysteine and glutathione-a non-enzymatic antioxidant. N-acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N-acetylcysteine role against reproductive toxicity in male Wistar rats (weight: 140-220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co-dosed with N-acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co-treatment with N-acetylcysteine significantly (p < .05) reversed perfluorooctanoic acid-mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle-stimulating hormone concentrations. N-acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co-treatment with N-acetylcysteine mitigated perfluorooctanoic acid-induced alterations in sperm function parameters. N-acetylcysteine abated (p < .05) perfluorooctanoic acid-induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N-acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid-mediated histological injuries in rat. Cooperatively, N-acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ.

Oxido-inflammatory responses and histological alterations in rat lungs exposed to petroleum product fumes.

Petroleum products-petrol, kerosene, and diesel-composed of volatile organic constituents contribute to air pollution. Exposure of gas station attendants (GSAs) to petroleum products fumes (PPFs) may account for occupation-related predisposition to respiratory toxicity and disease pathogenesis. We simulated GSA exposure to PPF inhalation and examined their effect on oxido-inflammatory responses, toxicity, and histopathological alterations in rat lungs, following 8-hours daily exposure for 60 and 90 days. Reactive oxygen and nitrogen species (RONS), oxidative stress and inflammatory biomarkers, namely: superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), TNF-α, IL-1ß, xanthine oxidase (XO), nitric oxide (NO) activity were evaluated. Besides, histopathological examination of the lungs and trachea of exposed rats, PPF exposure resulted in significant (P < .05) increases in RONS, biomarkers of oxidative stress, pro-inflammation cytokines, and reduced (P < .05) GSH levels in rats, secondary to histopathological alteration in lungs and trachea cytoarchitecture examined in an exposure-duration-dependent manner. We conclude, therefore, that the observed biochemical and histological changes create a microenvironment that is permissive to diseases pathogenesis of the respiratory system via oxido-inflammatory mechanistic pathways.

Kolaviron ameliorates hepatic and renal dysfunction associated with multiwalled carbon nanotubes in rats.

The increase in the exposure to carbon nanotubes (CNTs) and their incorporation into industrial, electronic, and biomedical products have required several scientific investigations into the toxicity associated with CNTs. Studies have shown that the metabolism and clearance of multiwalled CNTs (MWCNTs) from the body involve biotransformation in the liver and its excretion via the kidney. Since oxidative stress and inflammation underlines the toxicity of MWCNT, we investigated the ameliorative effect of kolaviron (KV), a natural antioxidant and anti-inflammatory agent, on hepatorenal damage in rats. Exposure to MWCNTs for 15 days significantly increased serum activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase thereby suggesting hepatic dysfunction. Kidney function, which was monitored by urea and creatinine levels, was also impaired by MWCNTs. Additionally, MWCNTs markedly increased myeloperoxidase activity, nitric oxide level, reactive oxygen and nitrogen species, and tumor necrosis factor level in both tissues. However, KV in a dose-dependent manner markedly attenuated MWCNT-induced markers of hepatorenal function in the serum and MWCNT-associated inflammation in the liver and kidney. Also, MWCNTs elicited significant inhibition of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities. There was a significant diminution in glutathione level (GSH) and enhanced production of malondialdehyde (MDA) in MWCNTs-exposed rats. KV treatment was able to significantly increase the antioxidant enzymes and enhance the GSH level with a subsequent reduction in the MDA level. Taken together, KV elicited ameliorative effects against hepatorenal damage via its anti-inflammatory and antioxidant properties. Thus, KV could be an important intervention strategy for the hepatorenal damage associated with MWCNTs exposure.

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.

Protocatechuic acid ameliorates testosterone-induced benign prostatic hyperplasia through the regulation of inflammation and oxidative stress in castrated rats.

Protocatechuic acid (PA) is a polyphenol-recognized for its efficacy as an antioxidant-possesses anticancer, anti-inflammatory, antioxidant properties. The efficacy of PA in the management of benign prostatic hyperplasia (BPH) has not been investigated. Forty-two castrated rats (n = 7) were treated as follows: control (corn oil), BPH only received testosterone propionate (TP) (TP 3 mg/kg intraperitoneally), BPH + PA (TP 3 mg/kg + PA 40 mg/kg), BPH + finasteride (Fin) (TP 3 mg/kg + Fin 10 mg/kg), PA only (40 mg/kg: by gavage), and Fin only (10 mg/kg: by gavage) for 4 weeks. In BPH rats, there were significant (P < .05) increases in prostatic (250%) and organosomatic (280%) weights compared with controls. Cotreatment decreased prostatic weights by 19% (PA) and 21% (Fin). Markers of inflammation: myeloperoxidase activities increased in serum (148%) and prostate (70%), as well as nitric oxide levels serum (92%) and prostatic (95%). Proinflammatory cytokines interleukin-1ß and tumor necrosis factor-α increased by 3.6- and 2.8-fold. Furthermore, prostatic malondialdehyde, superoxide dismutase, and serum total acid phosphatase increased by 97%, 25%, and 48%, respectively. Histology revealed poor architecture and severe proliferation of the prostate in BPH rats. Inflammation and oxidative stress markers, as well as the histological alteration in BPH rats, was attenuated (P < .05) upon cotreatment with PA and comparable with Fin cotreatment. These results suggest that PA mitigates oxido-inflammatory responses and restored prostatic cytoarchitecture to levels comparable with control in rats induced with BPH.

Selenium attenuates diclofenac-induced testicular and epididymal toxicity in rats.

The adverse effect of diclofenac administration on the male reproductive organ in both humans and rats has been reported. Selenium, a trace element vital in nutrition, plays a significant part in cellular redox homeostasis, including male reproduction. However, the impact of selenium on male reproductive toxicity associated with diclofenac administration is lacking in the literature. The current investigation assessed the modulatory effects of selenium on diclofenac-mediated reproductive toxicity in rats. Rats were treated for fourteen consecutive days, either with diclofenac (10 mg/kg) or co-treated with selenium (0.125 and 0.25 mg/kg) body weight. Sperm parameters, enzymes of testicular function, luteinizing, follicle-stimulating hormone and testosterone were assessed in addition to oxidative stress indices and histopathological changes. Selenium significantly alleviated diclofenac-induced decreases in sperm count and motility, testicular function enzymes and levels of luteinizing hormone and testosterone in serum. Moreover, selenium co-administration at 0.125 and 0.25 mg/kg inhibited the diclofenac-induced decrease of antioxidant enzyme activities and increased oxidative stress parameters-lipid peroxidation, reactive nitrogen and oxygen species-in epididymis and testes of rats. Selenium (0.25 mg/kg) alone ameliorated diclofenac-mediated histological injuries in exposed rats. Collectively, selenium enhanced testicular and epididymal function in diclofenac-treated rats by suppressing nitrosative and oxidative stress in rats.

Gallic acid and omega-3 fatty acids mitigate epididymal and testicular toxicity in manganese-treated rats.

Environmental contamination by manganese is correlated with diverse health outcomes plus reproductive dysfunction. Dietary gallic acid (GA) and omega-3 fatty acids (ω-3-FA) are well reported to elicit beneficial health effects. Though, information on GA and ω-3-FA effects on manganese-induced reproductive toxicity is absent in literature. We examined the effect of GA or ω-3-FA on manganese-induced epididymal and testicular toxicity in rats, exposed to manganese (15 mg/kg b.w.) alone, in combination with GA (30 mg/kg b.w.) or ω-3-FA (20 mg/kg b.w.) by gavage for 14 consecutive days. GA or ω-3-FA significantly (p < .05) prevented manganese-mediated increase in lipid peroxidation, myeloperoxidase activity, reactive oxygen and nitrogen species production but increased antioxidant enzymes activities and glutathione level in epididymis and testes treated rats. GA or ω-3-FA enhanced the activities of testicular function marker enzymes, namely acid phosphatase (ACP), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and glucose-6-phosphate dehydrogenase (G6PD) in the treated rats. GA or ω-3-FA amelioration of manganese-induced decreases in follicle-stimulating hormone, luteinising hormone, and testosterone levels were complemented by increase (p < .05) sperm functional characteristics in treated rats. Conclusively, GA or ω-3-FA may serve as dietary supplements to improve male reproductive dysfunction associated with manganese toxicity.

Cadmium and nickel co-exposure exacerbates genotoxicity and not oxido-inflammatory stress in liver and kidney of rats: Protective role of omega-3 fatty acid.

The present study examined the influence of co-exposure to cadmium (Cd) and nickel (Ni) on hepatorenal function as well as the protective role of omega-3 polyunsaturated fatty acids (ω-3FA) in rats. The animals were exposed to Cd (5 mg/kg) and Ni (150 µg/L in drinking water) singly or co-exposed to both metals and ω-3FA at 20 mg/kg for 14 consecutive days. Results showed that hepatorenal injury resulting from individual exposure to Cd or Ni was not aggravated in the co-exposure group. Moreover, ω-3FA markedly abrogated the reduction in the antioxidant enzyme activities, the increase in reactive oxygen and nitrogen species, and lipid peroxidation induced by Cd and Ni co-exposure. Additionally, ω-3FA administration markedly suppressed the increase in hepatic and renal myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha, and interleukin-1 ß levels in the co-exposure group. Genotoxicity resulting from individual exposure to Cd or Ni was intensified in the co-exposure group. However, ω-3FA administration markedly ameliorated the genotoxicity and histological lesions in the co-exposure group. Taken together, co-exposure to Cd and Ni aggravated genotoxicity and not oxido-inflammatory stress in the liver and kidney of rats. ω-3FA abated hepatorenal injury and genotoxicity induced by Cd and Ni co-exposure in rats.

Fluoride and diethylnitrosamine coexposure enhances oxido-inflammatory responses and caspase-3 activation in liver and kidney of adult rats.

The present study investigated the impact of coexposure to fluoride and diethylnitrosamine (DEN) on hepatorenal function in adult rats. The animals were exposed to fluoride (15 mg/L in drinking water) and DEN (10 mg/kg) singly or coexposed to both compounds for 14 days. Results demonstrated that the fluoride or DEN mediated increase in hepatorenal toxicity was intensified in the coexposure group. Additionally, the decrease in antioxidant enzyme activities as well as the elevation in reactive oxygen and nitrogen species, and lipid peroxidation was markedly aggravated in rats coexposed to DEN and fluoride. Furthermore, the increase in levels of nitric oxide, tumor necrosis factor-α and interleukin-1ß, myeloperoxidase and caspase-3 activities as well as histological lesions was more pronounced in the liver and kidney of rats coexposed to DEN and fluoride. Conclusively, coexposure to fluoride and DEN exacerbated hepatorenal damage via enhancement of oxido-inflammatory responses and caspase-3 activation in rats.