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.

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.

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.

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.

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.

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.

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.

Cerium Oxide Nanoparticles Attenuate Oxidative Stress and Inflammation in the Liver of Diethylnitrosamine-Treated Mice.

The catalytic activity of cerium oxide nanoparticles (CeO2NPs) is responsible for its application as an antitumor agent. This activity may be due to its ability to switch between III and IV oxidation states thereby conferring pro- and antioxidant properties. This study was designed to assess the hepatoprotective potential of CeO2NPs in male BALB/c mice administered diethylnitrosamine (DEN). Thirty-six mice were divided equally into six groups and treated intraperitoneally with normal saline (control), DEN (200 mg/kg) alone, CeO2NPs 1 (100 µg/kg) + DEN (200 mg/kg), CeO2NPs 2 (200 µg/kg) + DEN (200 mg/kg), CeO2NPs 1 alone, and CeO2NPs 2 alone. Animals were pretreated with CeO2NPs daily for eight consecutive days, while DEN was administered 48 h before the animals were sacrificed. Administration of DEN caused a significant increase in serum alanine aminotransferase (ALT) and urea by 51% and 96%, respectively. Markers of oxidative stress (malondialdehyde) and inflammation (nitric oxide and myeloperoxidase) in hepatic tissues of DEN-treated mice were increased by 60%, 16%, and 38%, respectively. The activities of hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and level of reduced glutathione were significantly decreased in DEN-treated mice by 50%, 123%, 23%, 419%, and 78%, respectively. In addition, DEN increased the expression of hepatic Bcl2 and COX-2, while p53, Bax, and iNOS were mildly expressed. Pretreatment with CeO2NPs attenuated the activities of antioxidant enzymes and expression of Bcl2 and COX-2. Overall, CeO2NPs confers protection from DEN-induced liver damage via antioxidative activity.

Genetic and systemic toxicity induced by silver and copper oxide nanoparticles, and their mixture in Clarias gariepinus (Burchell, 1822).

Unanticipated increase in the use of silver (Ag) and copper oxide (CuO) nanoparticles (NPs) due to their antimicrobial properties is eliciting environmental health concern because of their coexistence in the aquatic environment. Therefore, we investigated the genetic and systemic toxicity of the individual NPs and their mixture (1:1) using the piscine micronucleus (MN) assay, haematological, histopathological (skin, gills and liver) and hepatic oxidative stress analyses [malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)] in the African mud catfish, Clarias gariepinus. The fish were exposed to sublethal concentrations (6.25-100.00 mg/L) of each NP and their mixture for 28 days. Both NPs and their mixture induced significant (p < 0.05) increase in MN frequency and other nuclear abnormalities. There was significant decrease in haemoglobin concentration, red and white blood cell counts. Histopathological lesions observed include epidermal skin cells and gill lamellae hyperplasia and necrosis of hepatocytes. The levels of MDA, GSH and activities of SOD and CAT were impacted in C. gariepinus liver following the exposure to the NPs and their mixture. Interaction factor analysis of data indicates antagonistic genotoxicity and oxidative damage of the NPs mixture. These results suggest cytogenotoxic effects of Ag NPs, CuO NPs and their mixture via oxidative stress in Clarias gariepinus.

Evaluation of cytogenotoxicity and oxidative stress parameters in male Swiss mice co-exposed to titanium dioxide and zinc oxide nanoparticles.

A number of studies have investigated the adverse toxic effects of titanium dioxide (TiO2) nanoparticles (NPs) or zinc oxide (ZnO) NPs. Information on the potential genotoxic effects of the interactions of TiO2 NPs and ZnO NPs in vivo is lacking. Therefore, this study was designed to investigate the cytogenotoxicity of TiO2 NPs or ZnO NPs alone or their mixtures using the bone marrow micronucleus assay, and mechanism of damage through the evaluation of oxidative stress parameters in the liver and kidney tissues of Swiss mice. Intraperitoneal administration of doses between 9.38 and 150.00 mg/kg of TiO2 NPs or ZnO NPs or TiO2 NPs + ZnO NPs was performed for 5 and 10 days, respectively. TiO2 NPs alone induced a significant (P <  0.05) increase in micronucleated (Mn) polychromatic erythrocytes (PCEs) at the applied doses compared with the negative controls, with a significant difference between 5 and 10 days for TiO2 NPs alone and TiO2 NPs + ZnO NPs. Concurrently, TiO2 NPs alone for 5 days and TiO2 NPs and TiO2 NPs + ZnO NPs for 10 days significantly (P <  0.05) decreased the percentage PCE: normochromatic erythrocyte (NCE) indicating cytotoxicity; with a significant difference between the two periods. Significant (P <  0.001) changes in the activities of superoxide dismutase (SOD) and catalase (CAT), and levels of reduced glutathione (GSH) and malondialdehyde (MDA) were observed in the liver and kidney of mice exposed to TiO2 NPs or ZnO NPs alone or their mixtures. These results suggest that TiO2 NPs alone was genotoxic; TiO2 NPs and TiO2 NPs + ZnO NPs were noticeably cytotoxic while ZnO NPs was not cytogenotoxic. The individual NPs or their mixtures induced oxidative stress.

Root bark extract of Calliandra portoricensis (Jacq.) Benth. chemoprevents N-methyl-N-nitrosourea-induced mammary gland toxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Calliandra portoricensis (CP) is a herb widely used in Nigeria for the treatment of breast engorgement. However, the scientific evidence of this use and its mechanisms of action is not clearly understood. AIM OF THE STUDY: We assessed the chemopreventive effects of methanol extract of CP on N-methyl-N-nitrosourea (NMU)-induced mammary gland toxicity in rats. MATERIALS AND METHODS: Fingerprinting of methanol extract of CP by Gas Chromatography-Mass Spectrometry (GC-MS) was done. Female Wistar rats were assigned into eight groups: Group 1 (control), group 2 received NMU only, groups 3, 4 and 5 received NMU and treated with CP at doses of 100, 200 and 300 mg/kg, respectively. Group 6 received CP (300 mg/kg), group 7 received NMU and vincristine, while group 8 received vincristine. RESULTS: The weight-gain by rats decreased in all groups that received NMU. Administration of NMU significantly increased organo-somatic weight of mammary gland by 52%. The NMU increased serum nitric oxide, total bilirubin, mammary myeloperoxidase and lipid peroxidation by 76%, 87%, 130% and 21%, respectively, as well as activities of serum aspartate aminotransferase and lactate dehydrogenase. Also, NMU-treated rats had decreased total sulphydryl, reduced glutathione and catalase. Immunohistochemistry revealed strong expression of estrogen, progesterone and EGFR-2 proteins in NMU-treated rats. Treatment with CP (200 and 300 mg/kg) attenuated NMU-induced inflammation and oxidative stress. CONCLUSION: CP ameliorated NMU-induced toxicity by modulating different cellular targets.

Hexane fraction of Annona muricata (Sour sop) seed ameliorates testosterone-induced benign prostatic hyperplasia in rats.

BACKGROUND: Annona muricata is used in traditional African medicine to manage urinary obstruction. In this study, we hypothesized that hexane fraction of Annona muricata (HFAM) seeds will ameliorate testosterone propionate (Tp)-induced benign prostatic hyperplasia (BPh). METHODS: Castrated rats were assigned into six groups: non-castrated control, castrated control, castrated rats that received Tp (BPh group), [BPh+HFAM], [BPh+HFAM + finasteride], [BPh + finasteride]. RESULTS: The BPh rats had 3.8 and 3.9 folds increases in prostatic and organo-somatic weight, while treatment with HFAM alone and [HFAM + finasteride] decreased prostatic weight by 22% and 34%, respectively. BPh increased the activities of serum and prostatic total acid phosphatase by 95% and 121%; and activities of serum and prostatic alkaline phosphatase by 54% and 281%, respectively. Serum and prostatic lipid peroxidation were increased by 44% and 82%, respectively, in BPh rats with a concomitant decrease in prostatic superoxide dismutase by 73%. In BPh rats, serum and prostatic myeloperoxidase increased by 4.0 and 2.0 folds, while serum nitric oxide increased by 2.4 folds, respectively. Strong expression of inducible nitric oxide synthase, Bcl2, beta-catenin, androgen and estrogen receptors were observed in BPh rats. Importantly, treatment with HFAM or finasteride (or combination) attenuated prostatic weight, inflammatory and antioxidant indices in BPh rats. CONCLUSION: HFAM may serve as novel therapeutic agent against BPh.

Biochemical, Hormonal and Histological Changes in Prostate of Wistar Rats Following Long Term Streptozotocin-induced Diabetes Mellitus.

Diabetes mellitus (DM) is characterized by hyperglycemia and endocrine disorder. Diabetes mellitus is knownto promote male infertility by affecting sperm quality through altered steroidogenesis. The role of prostatic fluid in maintenance of sperm quality have been established. However, the effect of DM on prostate health is poorly understood.This study was designed to investigate the biochemical, hormonal and histological changes in prostate of male Wistar ratsafter 3- and 5-months DM. Twenty-six adult male Wistar rats were assigned into three groups. Group I (non-diabetic rats)served as control (n=10), out of which five rats (n=5) were sacrificed as control for 3-month study and the remaining animals(n=5) as control for 5-month study. Group II served as 3-month DM (n=8) and group III served as 5-month DM (n=8).Diabetes mellitus was induced by administration of a single dose of streptozotocin (STZ) (35 mg/kg i.p.). Rats were sacrificedat 3- and 5- months after DM. Biochemical indices in serum and prostate, histological and immunohistochemical studies ofthe prostate were evaluated. Results indicated that the weight of prostate of 3- and 5-months DM rats significantly (p<0.05)decreased by 33% and 59%, respectively. Fasting blood glucose, plasma glycated haemoglobin and number ofmicronucleated polychromatic erythrocytes in the bone marrow significantly (p<0.05) increased in 3- and 5-months DM.Activities of serum alanine and aspartate aminotransferases significantly (p<0.05) increased in 3 months DM withconcomitant increase in serum total bilirubin and urea in both models. The activities of total acid phosphatase in 3- and 5-months DM decreased by 34% and 76%, respectively while prostatic acid phosphatase decreased by 48% in 5-months DM.Prostatic zinc and bicarbonate increased in 3-months DM by 1.7 and 1.9 folds, and in 5-months DM by 5.8 and 1.7 folds,respectively. The levels of serum luteinizing and follicle stimulating hormones and testosterone decreased in both models.Prostatic lipid peroxidation increased while activities of antioxidative enzymes decreased in both models. Histology revealedhyperplasia, intra-luminal budding of epithelia, mild expressions of Bcl2 and Ki67 in 3- and 5-months DM. Overall, prostate health was compromised and may increase infertility in diabetic animals.

Methyl jasmonate reduces testosterone-induced benign prostatic hyperplasia through regulation of inflammatory and apoptotic processes in rats.

BACKGROUND: Phytotherapy is becoming a treatment option in management of diseases including benign prostatic hyperplasia (BPH). We have shown previously that methyl jasmonate (MeJA) ameliorated BPH, however the underlying mechanism of action remains unknown. This study was designed to investigate in mechanistic terms the protective role of MeJA in BPH. METHODS: BPH was induced by daily injections of testosterone propionate (TP) (3mg/kg) for 28 days. RESULTS: The weight and organo-somatic weight of prostate in BPH rats were 6.8 and 5.1 times higher than castrated-control group, respectively. Inflammatory markers; prostatic myeloperoxidase and total nitric oxide were significantly increased in BPH group. The activity of aniline hydroxylase (Phase I drug metabolizing enzyme) was significantly increased in BPH rats by 22%. In BPH group, immuno-histochemistry revealed strong expression of prostatic inducible nitric oxide synthase, cyclooxygenase-2 and Bcl2, while mild expression of p53 and Bax were seen. Serum triglyceride and total cholesterol were significantly increased, while HDL-c was decreased in BPH. Interestingly, MeJA and finasteride (singly or combination) attenuated inflammatory indices and induced apoptotic parameters in BPH rats. CONCLUSION: MeJA protects against TP-induced BPH via mechanisms that involve anti-inflammation, induction of apoptosis and inhibition of phase I drug metabolizing enzyme.

Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells.

Prostate cancer (PCa) is an international health problem and search for its effective treatment is in progress. Punicalagin (PN), polyphenol from pomegranate fruit, is known to exhibit potent anticancer activity in lung, breast and cervical cells. However, there is paucity of information on its effect in PCa. This study evaluated anti-proliferative effects of PN and its effects on extrinsic pathway of apoptosis in PCa cells, and angiogenesis in chicken chorioallantoic membrane (CAM). Antioxidant activities of PN were determined by 2,2-diphenyl-1-picryhydrazyl (DPPH) radical scavenging and inhibition of lipid peroxidation (LPO) methods. PCa (PC-3 and LNCaP) and normal prostate (BPH-1) cells were cultured and treated with PN (10, 50 and 100 µM). Cytotoxicity and viability effects of PN were determined by lactate dehydrogenase (LDH) and XTT assays, respectively. Antiangiogenic effects were measured using CAM assay, while apoptosis was assessed by DNA fragmentation, enrichment factor by Cell Death Detection ELISA kit and expressions of caspases-3 and -8. Results showed that PN (10-200 µM) significantly scavenged DPPH and inhibited LPO in a concentration-dependent manner. Furthermore, PN (10-100 µM) concentration-dependently inhibited viability in PC-3 and LNCaP, while viability in BPH-1 was insignificantly affected. PN had low toxicity on cells in vitro at concentrations tested. Also, PN (100 µM) increased enrichment factor in PC-3 (2.34 ± 0.05) and LNCaP (2.31 ± 0.26) relative to control (1.00 ± 0.00). In addition, PN (50 µM) decreased the network of vessels in CAM, suggesting its anti-angiogenic effect. Moreso, PN increased the expressions of caspases-3 and -8 in PC-3. Overall, PN exerts anti-proliferative activity in PCa cells via induction of apoptosis and anti-angiogenic effect.

Antioxidant and antiproliferative potentials of methanol extract of Xylopia aethiopica (Dunal) A. Rich in PC-3 and LNCaP cells.

BACKGROUND: Our previous studies showed that fruit methanol extract from Xylopia aethiopica (MEXA) exhibited antiproliferative activity in human cervical cancer cells via the induction of apoptosis. The present study was designed to assess the antiproliferative, antiangiogenic and antioxidant effects of MEXA on prostate cancer (PCa) cells (PC-3 and LNCaP). METHODS: PC-3 and LNCaP cells were cultured and treated with MEXA (10, 50 and 100 µg/mL). The sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) and lactate dehydrogenase (LDH) assays were used to evaluate cell viability and cytotoxicity, respectively. DNA fragmentation was determined by cell death detection ELISA plus, and angiogenesis was assessed by chicken chorioallantoic membrane (CAM) assay. The antioxidant activities of MEXA were determined by DPPH and hydroxyl (OH) radicals' scavenging methods as well as through the inhibition of lipid peroxidation (LPO) in rats' liver homogenate. RESULTS: MEXA at 100, 250 and 500 µg/mL scavenged DPPH by 48%, 62%, 70% and OH radical by 39%, 58%, 67%, respectively. MEXA significantly (p<0.05) inhibited LPO in a concentration-dependent manner. In addition, MEXA had antiproliferative effects on PC-3 and LNCaP with IC50 of 62.1 and 73.6 µg/mL, respectively, at 96 h. The LDH assay showed that MEXA had low toxicity in vitro at its IC50 values. The extent of DNA fragmentation by MEXA showed higher values in PC-3 and LNCaP, suggesting the possible induction of apoptosis. In contrast, MEXA did not affect the network of vessels in CAM, thus lacking anti-angiogenic property. CONCLUSIONS: These findings suggest that MEXA induces antiproliferative activity in PCa cells through a mechanism that involves apoptosis. Therefore, MEXA may be a potential therapeutic agent for PCa.

Betulinic acid protects against N-nitrosodimethylamine-induced redox imbalance in testes of rats.

OBJECTIVES: N-nitrosodimethylamine (NDMA) is known to elicit carcinogenic activity in the liver and kidney of animals. There is a dearth of information of its effect in testis. This study evaluated the protective role of betulinic acid (BA) against NDMA-induced redox imbalance in testes of rats. METHODOLOGY: Twenty-four male rats were assigned into four groups and treated with normal saline, BA, NDMA and [BA+NDMA]. BA (25 mg/kg) was given for 14 days, while NDMA (5 mg/kg) was given on days 7 and 12. RESULTS: Administration of NDMA significantly increased the weight and relative weight of testes by 51 and 71%, respectively, while treatment with BA attenuated the weight-gain. Furthermore, NDMA decreased the sperm count, motility and live-dead ratio by 57, 36 and 37%, respectively, and increased total sperm abnormality by 56%. However, BA attenuated the changes in the spermiogram of NDMA-treated rats. NDMA significantly decreased the activities of antioxidative enzymes, follicle-stimulating and luteinizing hormones, while testicular levels of thiobarbituric acid reactive substances and total cholesterol were increased. Also, NDMA increased the activities of aniline hydroxylase and aminopyrine-N-demethylase. Supplementation with BA attenuated NDMA-induced alteration in these biochemical indices. CONCLUSION: BA protects against NDMA-induced redox imbalance via activation of antioxidative pathway.

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.

Ameliorative Effects of Kolaviron, a Biflavonoid Fraction from Garcinia Kola Seed, on Hepato-renal Toxicity of Anti-tuberculosis Drugs in Wistar Rats.

BACKGROUND: Tuberculosis (TB) is an infectious disease of international health priority. The combination of anti-TB drugs (4-Tabs)- isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (ETB) are effective in the management of the disease, however, their toxic effect is a major concern. PURPOSE: The study was designed to evaluate the toxicity of anti-TB drugs in male Wistar rats and possible ameliorative effects of kolaviron (KV), a biflavonoid from Garcinia kola seeds. METHODS: Twenty-eight rats were assigned into four groups; Group 1 (Control) received corn oil, Group 2 (4-Tabs) received therapeutic doses of INH (5 mg/kg), RIF (10 mg/kg), PZA (15 mg/kg) and ETB (15 mg/kg) in combination, Group 3 (4-Tabs + KV) received INH, RIF, PZA, ETB and KV (200 mg/kg) and Group 4 (KV) received KV (200 mg/kg) by oral gavage three times per week for 8 consecutive weeks. RESULTS: Administration of 4-Tabs caused oxidative stress resulting in significant (p = 0.031, 0.027) increase in malondialdehyde levels in the liver and kidney of rats by 101% and 34%, respectively. Also, 4-Tabs caused significant (p = 0.023-0.035) elevation of serum alanine and aspartate aminotransferases by 41% and 48%, creatinine by 252% and total bilirubin by 89%, respectively. In contrast, hepatic and renal antioxidant indices- reduced glutathione, glutathione peroxidase, glutathione-s-transferase and superoxide dismutase were significantly (p = 0.028-0.039) decreased in 4-Tabs-treated rats. Co-administration of KV with 4-Tabs significantly restored the antioxidant parameters and biochemical indices to near normal. CONCLUSION: These findings suggest that anti-TB drugs elicit oxidative damage in liver and kidney of rats while KV protects against the adverse effects via antioxidative mechanism.