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.

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.

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.

Biflavonoid fraction from Garcinia kola seed ameliorates hormonal imbalance and testicular oxidative damage by anti-tuberculosis drugs in Wistar rats.

BACKGROUND: Tuberculosis (TB) is a global health problem. The effects of anti-TB drugs on male reproductive system have not been properly evaluated. We investigated the effects of anti-TB drugs on testicular antioxidant indices, sperm characteristics and hormonal levels in rats, and the protective role of kolaviron (KV), a biflavonoid from Garcinia kola seed. METHODS: Twenty-eight male Wistar rats were assigned into four groups and orally treated with corn oil (control), anti-TB drugs [4-Tabs=isoniazid (5 mg/kg), rifampicin (10 mg/kg), pyrazinamide (15 mg/kg) and ethambutol (15 mg/kg) in combination], anti-TB drugs +KV and KV alone (200 mg/kg). Anti-TB drugs and KV were given three times per week for 8 weeks. In vitro, reducing power, inhibition of lipid peroxidation (LPO), diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging effects of KV were examined. RESULTS: KV at 10, 20, 50 and 100 µg/mL showed strong reducing potential and effectively scavenged DPPH and OH radicals in a concentration-dependent manner. Furthermore, KV significantly inhibited LPO in rats' liver homogenate. In vivo, administration of 4-Tabs caused a significant (p<0.05) decrease in body weight gain and weight of testis of rats. Body weight gain and weight of testis decreased by 45% and 36%, respectively, in the 4-Tabs-treated rats. Also, 4-Tabs increased testicular lipid peroxidation by 82%, with a concomitant decrease in antioxidant indices. Testicular reduced glutathione, superoxide dismutase and glutathione peroxidase decreased by 2.2-, 1.9- and 1.6-folds, respectively. Likewise, 4-Tabs markedly decreased sperm count, motility, luteinizing hormone and testosterone. Co-administration of KV with 4-Tabs normalized body weight, enhanced antioxidant system and improved sperm characteristics. CONCLUSIONS: Kolaviron protects male reproductive system from oxidative damage by anti-tuberculosis drugs via the antioxidative mechanism.

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.