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.

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.

Physiological and histopathological alterations in male Swiss mice after exposure to titanium dioxide (anatase) and zinc oxide nanoparticles and their binary mixture.

Existing studies have shown the systemic damage of titanium dioxide (TiO2) or zinc oxide (ZnO) nanoparticles (NPs), but there is little or no existing knowledge on the potential adverse toxic effects of the mixture of the two. In order to investigate the in vivo toxic effect of the mixture of TiO2 NPs and ZnO NPs, the acute toxicities of TiO2 NPs, ZnO NPs by themselves, and their mixture (1:1) were determined. The systemic toxicities of the individual NPs and mixture were evaluated in mice using hematological indices, hepatic, renal, and lipid profile parameters, and histopathology as endpoints. NPs were intraperitoneally administered at doses of 9.38, 18.75, 37.50, 75.00, and 150.00 mg/kg bw each. Individual NPs and their mixture were administered daily for 5 and 10 d, respectively. The LD50 of ZnO NPs was 299.9 mg/kg while TiO2 NPs by themselves or TiO2 NPs + ZnO NPs were indeterminate due to the absence of mortality of the male mice treated. TiO2 NPs, ZnO NPs by themselves and TiO2 NPs + ZnO NPs induced significant alterations in the hematological and biochemical parameters, with higher toxicity at 10 d. Histopathological lesions were observed in the liver, kidneys, spleen, heart, and brain of mice treated with the individual NPs and their mixture. TiO2 NPs + ZnO NPs were able to induce a higher systemic toxicity than TiO2 NPs or ZnO NPs individually. Our data suggest that more comprehensive risk assessments should be carried out on the mixture of NPs before utilization in consumer products.

Betulinic acid abates N-nitrosodimethylamine-induced changes in lipid metabolism, oxidative stress, and inflammation in the liver and kidney of Wistar rats.

N-nitrosamines have been linked with cancer in humans due to their presence in drinking water and diets. This study evaluated the role of betulinic acid (BA) in abating oxidative stress, inflammation, and hyperlipidemia in rats treated with N-nitrosodimethylamine (NDMA). Twenty-four male rats were assigned into four equal groups. Group I served as the control, Group II received BA (25 mg/kg), Group III received NDMA (5 mg/kg) and, Group IV received BA (25 mg/kg) and NDMA (5 mg/kg). Results showed that the administration of NDMA significantly (p < 0.05) elevated malondialdehyde in the liver and kidney relative to controls. Activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, and the level of glutathione were significantly (p < 0.05) decreased by NDMA, while treatment with BA elevated the activities of these enzymes in the liver and kidney. The BA lowered serum interleukin-6 and tumor necrosis factor-alpha levels against the NDMA effect. Furthermore, NDMA increased hepatic and renal triglyceride while phospholipids levels were decreased. NDMA significantly modulated the activities of drug-metabolizing enzymes (aniline hydroxylase, aminopyrine-N-demethylase, and uridyldiphosphoglucuronyltransferase), while BA was able to restore these enzymes to values close to controls. Histology revealed the presence of infiltration and fibroplasia in the liver, while cortical degeneration was noticed in the kidney in NDMA-administered rats. These lesions were reduced in the NDMA rats treated with BA. The findings suggest that BA improves NDMA-induced damage in the liver and kidney of rats through reactions that can be linked with antioxidant, anti-inflammatory, and lipid-lowering pathways.

Cerium oxide nanoparticles elicit antitumourigenic effect in experimental breast cancer induced by N-methyl-N-nitrosourea and benzo(a)pyrene in female Wistar rats.

The use of cerium oxide nanoparticles [CeO2 NPs] in the biomedical field has continued to gain prominence due to its potent antioxidant property. This study was designed to assess the antitumorigenic effect of CeO2 NPs in rats administered N-methyl-N-nitrosourea [NMU] and benzo(a)pyrene (BaP). Twenty four female Wistar rats were equally assigned into four groups and treated with normal saline (control), [NMU + BaP], [NMU + BaP+CeO2 NPs], and [NMU + BaP + vincristine]. Animals were pretreated with NMU and BaP three times (age 7, 10, and 13 weeks). Thereafter, vincristine and CeO2 NPs were administered twice and three times per week, respectively, for 13 weeks. Results showed that the administration of NMU and BaP increased serum nitric oxide [NO] and myeloperoxidase [MPO] by 220% and 132%, respectively, whereas the activities of aspartate and alanine aminotransferases and level of total bilirubin remained unchanged. Furthermore, mammary inflammatory [NO and MPO] and oxidative stress (LPO) markers were increased by 37%, 19%, and 24%, respectively. Mammary superoxide dismutase, catalase, reduced glutathione, and glutathione-S-transferase were significantly decreased in [NMU + BaP]-administered rats by 165%, 146%, 35%, and 36%, respectively. Immunohistochemistry showed downregulation of Bax, p53, and caspase-3, while histology revealed the presence of malignant epithelial cells with pyknotic nuclei and high nucleocytoplasm in [NMU + BaP]-administered rats. Treatment with CeO2 NPs attenuated oxidative stress, apoptosis, and inflammation and restored the cytoarchitecture of the tissue. Overall, CeO2 NPs show an antitumourigenic effect in experimental breast cancer by targeting pathways linked to inflammation and apoptosis.

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.

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.

Alteration of sperm parameters and reproductive hormones in Swiss mice via oxidative stress after co-exposure to titanium dioxide and zinc oxide nanoparticles.

In this study, Swiss male mice were intraperitoneally administered with titanium dioxide (TiO2 ) and zinc oxide (ZnO) nanoparticles (NPs) and their mixture (1:1) at doses between 9.38 and 75 mg/kg for 5 weeks to evaluate reproductive toxicity. Both NPs and their mixture significantly (p < .001) altered sperm motility, reduced sperm numbers and increased abnormalities, while their mixture induced more sperm abnormalities than either TiO2 NPs or ZnO NPs. Both NPs and their mixture significantly (p < .05) reduced the LH level, while ZnO NPs alone and their mixture (p < .001) increased the testosterone levels at tested doses. The testes of exposed mice showed pathological changes and altered histomorphometrics. TiO2 NPs and ZnO NPs individually induced a significant (p < .01) reduction in SOD and CAT activities, while the mixture significantly (p < .001) decreased CAT activity and increased SOD activity. TiO2 NPs alone at 9.38 mg/kg induced a significant (p < .001) reduction in the GSH level, while both NPs and their mixture increased the MDA level significantly (p < .05). The data showed that the mixture had a synergistic interaction to induce testicular damage. Overall, oxidative stress may be involved in the NP-mediated testicular damage observed.

Enhanced production of succinic acid from methanol-organosolv pretreated Strophanthus preussii by recombinant Escherichia coli.

A biorefinery process for high yield production of succinic acid from biomass sugars was investigated using recombinant Escherichia coli. The major problem been addressed is utilization of waste biomass for the production of succinic acid using metabolic engineering strategy. Here, methanol extract of Strophanthus preussii was used for fermentation. The process parameters were optimized. Glucose (9 g/L), galactose (4 g/L), xylose (6 g/L) and arabinose (0.5 g/L) were the major sugars present in the methanol extract of S. preussii. E. coli K3OS with overexpression of soluble nucleotide pyridine transhydrogenase sthA and mutation of lactate dehydrogenase A (ldhA), phosphotransacetylase acetate kinase A (pta-ackA), pyruvate formate lyase B (pflB), pyruvate oxidase B (poxB), produced a final succinic acid concentration of 14.40 g/L and yield of 1.10 mol/mol total sugars after 72 h dual-phase fermentation in M9 medium. Here, we show that the maximum theoretical yield using methanol extracts of S. preussii was 64%. Hence, methanol extract of S. preussii could be used for the production of biochemicals such as succinate, malate and pyruvate.

Methyl Jasmonate Ameliorates Testosterone Propionate-induced Prostatic Hyperplasia in Castrated Wistar Rats.

Benign prostate hyperplasia (BPH) is a progressive disease that is related to age. Known therapeutic agents used in the treatment of BPH are associated with toxicity. Therefore, chemoprevention could be an effective approach. We investigated the ameliorative effects of methyl jasmonate (MeJA) in testosterone propionate (TP)-induced BPH in castrated rats. Castration was performed by removing both testes through the scrotum sack under ketamine anesthesia. Rats were assigned into seven groups of seven animals each: non-castrated control, castrated control, castrated rats that received TP, castrated rats that received TP and MeJA, castrated rats that received TP and finasteride, castrated rats that received MeJA, and castrated rats that received finasteride. Results indicate that BPH rats had significantly (p < 0.05) elevated prostate weight and relative weight of prostate relative to control. Also, BPH rats had significantly (p < 0.05) increased activities of prostatic acid and alkaline phosphatases, levels of zinc, and malondialdehyde. Further, levels of enzymic and non-enzymic antioxidative indices were significantly (p < 0.05) reduced in BPH. Histology of prostate revealed hyperplasia of transition lobe, increased expression of PSA, and Ki67 in BPH. Treatment with MeJA and finasteride attenuated the activities of the phosphatases and levels of antioxidants in BPH. Overall, MeJA ameliorates BPH via antioxidative mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

Modulatory effects of methanol extract of Artocarpus altilis (Moraceae) on cadmium-induced hepatic and renal toxicity in male Wistar rats.

BACKGROUND: Cadmium (Cd) is an environmental risk factor with an established toxicity in animals. Therefore, natural antioxidants may be protective against Cd-toxicity. The study was designed to investigate the modulatory effects of methanol extract of Artocarpus altilis (AA) on oxidant-antioxidant balance and lipid profile in liver and kidney of Cd-exposed rats while quercetin (QE) served as standard. METHODS: Total phenolic content (TPC) and 2,2-diphenyl-1-picryldydrazyl (DPPH) radical scavenging activity of AA were assessed in vitro. In vivo, rats were orally treated with AA (200mg/kg) and QE (25mg/kg) daily for three weeks and challenged with two doses of Cd (1.5mg/kg, i.p.) in the last 72h. RESULTS: The TPC and DPPH scavenging effects of AA were high and comparable with catechin. Cd-intoxication significantly (p<0.05) increased the activities of serum alanine aminotransferase and levels of urea, total bilirubin and creatinine by 94%, 60%, 234% and 76%, respectively. Cd-exposure caused a significant increase (p<0.05) in serum and tissues total cholesterol, triglyceride, low-density lipoprotein-cholesterol and reduction in high-density lipoprotein-cholesterol levels. The levels of hepatic and renal antioxidant parameters: glutathione-s-transferase, superoxide dismutase and reduced glutathione were significantly (p<0.05) decreased in Cd-intoxicated rats with concomitant elevation of lipid peroxidation. Histopathological findings revealed necrosis and distortion of architecture of renal tissue and, periportal infiltration in hepatocytes of Cd-intoxicated rats. Pretreatment with AA and QE restored antioxidant status, lipid profile and attenuated the lesions in the tissues. CONCLUSIONS: Extract of A. altilis protects against Cd-induced liver and kidney dysfunction via antioxidant and radical scavenging activities.

Effect of chloroquine, methylene blue and artemether on red cell and hepatic antioxidant defence system in mice infected with Plasmodium yoelii nigeriensis.

Reactive oxygen species are mediators of tissue injury and are involved in malaria infection. In this study, the status of red cell and hepatic oxidative stress and antioxidant defence indices were investigated during Plasmodium yoelii nigeriensis (P. yoelii) infection, and treatment with chloroquine (CQ), methylene blue (MB) or artemether (ART) in mice. P. yoelii infection caused a significant (p < 0.05) increase in oxidative stress as evidenced by the elevated level of malondialdehyde. This was followed by a significant decrease (p < 0.05) in hepatic antioxidant defence indices, viz. reduced glutathione (GSH) and glutathione-S-transferase (GST). Also, the red cell catalase activity was significantly (p < 0.05) lower in malaria infection, while there was no significant difference (p > 0.05) in the superoxide dismutase (SOD) activity of infected mice when compared to untreated normal. Treatment of infected mice with the three antimalarials showed that the drugs suppressed the parasitaemia in the order CQ > ART > MB. CQ, MB and ART treatment of infected mice caused a significant (p < 0.05) increase in the levels of hepatic GSH and GST. Specifically, CQ, MB and ART increased the levels of hepatic GSH by 108, 124 and 98 %, respectively, at day 6. Also, ART treatment of infected mice significantly (p < 0.05) elevated the red cell SOD level by 200 % at day 3. Taken together, the findings suggest that the antimalarial effect of CQ, MB and ART countered the P. yoelii-induced oxidative stress leading to the elevation of enzymatic and non-enzymatic antioxidants in the host system.

Combined cerium and zinc oxide nanoparticles induced hepato-renal damage in rats through oxidative stress mediated inflammation.

The toxicity profiles of nanoparticles (NPs) used in appliances nowadays remains unknown. In this study, we investigated the toxicological consequences of exposure to cerium oxide (CeO2) and zinc oxide (ZnO) nanoparticles given singly or in combination on the integrity of liver and kidney of male Wistar rats. Twenty (20) rats were allotted into four groups and treated as: Control (normal saline), CeO2NPs (50 µg/kg), ZnONPs (80 µg/kg) and [CeO2NPs (50 µg/kg) + ZnONPs (80 µg/kg)]. The nanoparticles were given to the animals through the intraperitoneal route, three times per week for four repeated weeks. Results revealed that CeO2 and ZnO NPs (singly) increased serum AST and ALT by 29% & 57%; 41% & 18%, and co-administration by 53% and 23%, respectively. CeO2 and ZnO NPs increased hepatic and renal malondialdehyde (MDA) by 33% and 30%; 38% and 67%, respectively, while co-administration increased hepatic and renal MDA by 43% and 40%, respectively. The combined NPs increased hepatic NO by 28%. Also, CeO2 and ZnO NPs, and combined increased BAX, interleukin-1ß and TNF-α by 45, 38, 52%; 47, 23, 82% and 41, 83, 70%, respectively. Histology revealed hepatic necrosis and renal haemorrhagic parenchymal in NPs-treated rats. Summarily, CeO2 and ZnO NPs produced oxidative injury and induced inflammatory process in the liver and kidney of experimental animals.

Effect of tenofovir, an antiretroviral drug, on hepatic and renal functional indices of Wistar rats: protective role of vitamin E.

BACKGROUND: Tenofovir (TFR) is a nucleotide reverse transcriptase inhibitor with activity against human immunodeficiency virus. We studied the effect of TFR administered to Wistar rats on hepatic and renal function markers and the possible modulatory role of vitamin E (Vit E). METHODS: The study consists of four groups of six rats each. The first group served as control, the second group received TFR at 50 mg/kg/day for 4 weeks, third group received TFR and Vit E, and the last group received Vit E alone. RESULTS: TFR administration caused a significant (p<0.05) increase in the levels of serum urea, creatinine, urinary glucose, and protein by 65%, 51%, 88%, and 79%, respectively, relative to controls. This was followed by a significant (p<0.05) reduction in creatinine clearance of TFR-treated rats. There were no significant differences (p>0.05) in the activities of serum aminotransferases, γ-glutamyltransferase, and alkaline phosphatase in TRF-treated rats relative to controls. TFR administration caused a marked elevation of malondialdehyde (MDA; index of lipid peroxidation) in the animals. Specifically, serum, hepatic, and renal MDA levels increased by 75%, 90%, and 102%, respectively. TRF-treated rats had significantly (p<0.05) reduced activities of renal catalase, glutathione-S-transferase, and superoxide dismutase. Supplementation of Vit E ameliorated TFR-induced effects by decreasing the levels of MDA and enhancing the activities of renal antioxidative enzymes. The biochemical data were supported by histopathological findings from the slides. CONCLUSIONS: TFR increased oxidative stress and altered kidney function markers in the rats, whereas supplementation of Vit E attenuated these effects.

Fraction from Calliandra portoricensis reduces 7, 12 dimethylbenz(a)anthracene-induced mammary tumors in Wistar rats.

Objective: Calliandra portoricensis (CP) is used in Nigeria for the treatment of breast diseases. We investigated the effects of fraction from CP on 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumors. Materials and Methods: Female Wistar rats (40) were allotted into five equal groups. Group 1 served as control, group 2 received DMBA (50 mg/kg), groups 3 and 4 received DMBA and were treated with CP at doses of 50 and 100 mg/kg respectively, and the group 5 received DMBA and vincristine (0.5 mg/kg). DMBA was injected intraperitoneally once while vincristine and CP were given twice and thrice per week, respectively. Results: Administration ofDMBA caused a significant decrease in body weight gain by 52%. In addition, DMBA significantly increased organo-somatic weight of mammary gland by 4.0 folds. Also, DMBA significantly increased inflammatory and oxidative stress markers serum interleukin-1ß (IL-1ß), lipid peroxidation (LPO) and myeloperoxidase (MPO) by 27, 18 and 435%, respectively. Similarly, mammary NO (nitric oxide) and LPO were increased by 468 and 21%, respectively. In contrast, DMBA decreased the levels of apoptotic markers BAX, caspases 3 and 9 by 20, 15 and 18%, and mammary superoxide dismutase (SOD), catalase (CAT) and glutathione-s-peroxidase (GPx) by 45, 51 and 68%, respectively. Histology revealed gland with malignant epithelial cells and high nucleo-cytoplasm in DMBA-administered rats. Treatment with CP 100 mg/kg decreased LPO, MPO, IL-1ß and NO by 28, 35, 78 and 85%, respectively, and ameliorated DMBA-induced cyto-architectural anomalies. Conclusion: Fraction of CP protects mammary gland from DMBA insults via antioxidative and anti-inflammatory mechanisms.

Evaluation of the antioxidative potential of diisopropyldithiocarbamates sodium salt on diclofenac-induced toxicity in male albino rats.

Diclofenac (DIC) is a non-steroidal anti-inflammatory drug (NSAID) which is known to induce oxidative stress. Dithiocarbamates are compounds with proven antioxidant effect. The aim of the present study was to investigate the antioxidant capacity of diisopropyldithiocarbamates sodium salt (a synthetized compound) (Na(i-Pr2dtc)) against diclofenac-induced toxicity in the testes of male Wistar albino rats. The animals were assigned into six groups of six rats each. Group 1 (control) received corn oil, Groups 2, 3, 4, 5, 6 received DIC (100 mg/kg), DIC and (Na(i-Pr2dtc) (30 mg/kg), DIC and vitamin E (30 mg/kg), (Na(i-Pr2dtc) (30 mg/kg) and vitamin E only respectively. Our findings show that treatment with DIC significantly reduced superoxide dismutase (SOD) activity by 42% compared to normal control (NC) animals. In DIC treated group, Na(i-Pr2dtc) caused a 17% elevation of catalase (CAT) activity compared to DIC only group. Reduced glutathione level was significantly reduced in DIC only treated group when compared with DIC and VIT E treated group. Photomicrographs of testis from Na(i-Pr2dtc) treated rats showed normal seminiferous epithelium with no lesions. In conclusion, Na(i-Pr2dtc) has antioxidant properties.

Methanolic extract of Cnidoscolus aconitifolius attenuates renal dysfunction induced by chronic ethanol administration in Wistar rats.

AIMS: The present work studied the modulatory role of methanolic extract of Cnidoscolus aconitifolius leaf (MECA) in rat model of renal dysfunction induced by chronic ethanol administration. METHODS: Forty-two male Wistar albino rats weighing between 170 and 180 g were distributed into seven groups of six animals each. Some groups were pretreated with MECA (100 and 200 mg/kg) or kolaviron (KV) (200 mg/kg) for 2 weeks before simultaneous administration of MECA or KV and 20% ethanol (7.9 g/kg) for eight consecutive weeks. Others were given ethanol or MECA (200 mg/kg) or KV alone, and the control received corn oil (Vehicle). KV served as the standard antioxidant. RESULTS: In ethanol-treated rats, serum urea, creatinine, urinary glucose, gamma-glutamyltransferase and protein increased by 59, 81, 70, 148 and 63%, respectively, while creatinine clearance significantly (P < 0.05) decreased by 79%. MECA significantly (P < 0.05) attenuated the above biochemical indices to near normal. Also, the levels of serum and kidney malondialdehyde (MDA) (Index of lipid peroxidation) increased by 102 and 143%, respectively, in ethanol-treated rats. Ethanol intoxication caused a significant (P < 0.05) decrease in the levels of catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) in kidney of the rats. MECA attenuated the ethanol-induced increases in serum and kidney MDA, and also enhanced the antioxidant status of the rats by increasing the levels of CAT, SOD and GSH. The activity of MECA was comparable with KV at 200 mg/kg. The biochemical findings were corroborated by histopathological examination of the kidney. CONCLUSION: The results suggest that the renal protective effect of C. aconitifolius leaf extract is by attenuating oxidative stress induced by chronic ethanol administration.

Cnidoscolus aconitifolius leaf extract protects against hepatic damage induced by chronic ethanol administration in Wistar rats.

AIMS: This study focused on the possible protective effect of Cnidoscolus aconitifolius leaf extract (CA) against hepatic damage induced by chronic ethanol administration in rats. METHODS: Male Wistar rats were distributed into seven groups of six rats each. The first group was the control, second group received 20% ethanol-only (7.9 g/kg), third and fourth groups were pre-treated with CA (100 and 200 mg/kg, respectively) before treatment with ethanol. The fifth and sixth groups received CA and kolaviron (KV; 200 mg/kg), respectively, while the seventh group received KV and ethanol. KV served as the reference antioxidant. RESULTS: Ethanol-treated rats had significantly (P < 0.05) elevated serum and liver post-mitochondrial malondialdehyde, an index of lipid peroxidation. Ethanol toxicity lowered the antioxidant defense indices, such as reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Specifically, the activities of hepatic SOD and CAT decreased by 48 and 51%, respectively, while the level of GSH decreased by 56%. In addition, serum total cholesterol, triglycerides and low-density lipoproteins-cholesterol levels were significantly (P < 0.05) elevated in ethanol-treated rats. Also, significant (P < 0.05) elevation in serum alanine and aspartate aminotransferases, and γ-glutamyl transferase activities were observed in ethanol-treated rats. Supplementation with CA significantly (P < 0.05) decreased the activities of liver marker enzymes, stabilized the lipid profiles and restored the antioxidants status of ethanol-treated rats. The activities of CA were comparable with KV in the ethanol-treated rats. This observation was supported by histopathological examination of liver slides. CONCLUSION: These findings suggest the hepatoprotective and antioxidant effects of CA leaf extract, which offered protection against ethanol-induced toxicity.

Antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (black cumin) in mice infected with Plasmodium yoelli nigeriensis.

The antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (MENS) were investigated against established malaria infection in vivo using Swiss albino mice. The antimalarial activity of the extract against Plasmodium yoelli nigeriensis (P. yoelli) was assessed using the Rane test procedure. Chloroquine (CQ)-treated group served as positive control. The extract, at a dose of 1.25 g/kg body weight significantly (p<0.05) suppressed P. yoelli infection in the mice by 94%, while CQ, the reference drug, produced 86% suppression when compared to the untreated group after the fifth day of treatment. P. yoelli infection caused a significant (p<0.05) increase in the levels of red cell and hepatic malondialdehyde (MDA), an index of lipid peroxidation (LPO) in the mice. Serum and hepatic LPO levels were increased by 71% and 113%, respectively, in the untreated infected mice. Furthermore, P. yoelli infection caused a significant (p<0.05) decrease in the activities of superoxide dismutase, catalase, glutathione-S-transferase and the level of reduced glutathione in tissues of the mice. Treatment with MENS significantly (p<0.05) attenuated the serum and hepatic MDA levels in P. yoelli-infected mice. In addition, MENS restored the activities of red cell antioxidant enzymes in the infected mice to near normal. Moreover, MENS was found to be more effective than CQ in parasite clearance and, in the restoration of altered biochemical indices by P. yoelli infection. These results suggest that N. sativa seeds have strong antioxidant property and, may be a good phytotherapeutic agent against Plasmodium infection in malaria.

Antiproliferative action of Xylopia aethiopica fruit extract on human cervical cancer cells.

The anticancer potential of Xylopia aethiopica fruit extract (XAFE), and the mechanism of cell death it elicits, was investigated in various cell lines. Treatment with XAFE led to a dose-dependent growth inhibition in most cell lines, with selective cytotoxicity towards cancer cells and particularly the human cervical cancer cell line C-33A. In this study, apoptosis was confirmed by nuclear fragmentation and sub-G(0)/G(1) phase accumulation. The cell cycle was arrested at the G(2)/M phase with a decreased G(0)/G(1) population. A semi-quantitative gene expression study revealed dose-dependent up-regulation of p53 and p21 genes, and an increase in the Bax/Bcl-2 ratio. These results indicate that XAFE could be a potential therapeutic agent against cancer since it inhibits cell proliferation, and induces apoptosis and cell cycle arrest in C-33A cells.