Carnosine Remedial Effect on Fertility of Male Rats Receiving Cyclophosphamide, Hydroxydaunomycin, Oncovin and Prednisone (CHOP).

Chemotherapeutic agents can impair gonadal function triggering infertility. Here, we probed the properties of carnosine as an antioxidant in reproductive disorders caused by the combination of cyclophosphamide, hydroxydaunomycin (doxorubicin), oncovin (vincristine) and prednisone (CHOP); this combination is mostly used in treating non-Hodgkin lymphoma. Animals were distributed into four groups: Group I was the control. Group II received carnosine (250mg kg day-1 , i.p.); Group III received CHOP: cyclophosphamide (27 mg/kg/cycle), doxorubicin (1.8 mg/kg/cycle) and vincristine (0.05 mg/kg /cycle) by i.p. plus oral prednisone (1.47 mg kg-1  day-1 /cycle) for five days. Group IV received carnosine plus CHOP. The study involved 4 cycles each of 3 weeks. Also, we explored the effect of combining carnosine with CHOP on the development of solid Ehrlich carcinoma in mice. CHOP lowered genitals weight, sperm count and motility, testicular function marker enzymes, serum testosterone level and gene expression of 3ß-hydroxysteroid dehydrogenase, 17ß-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein. Furthermore, CHOP elevated testicular oxidative stress, serum follicle-stimulating hormone, luteinising hormone and triggered DNA damage. Morphometric and histopathological examinations of testicular tissues buttressed the biochemical results. Importantly, administration of carnosine ameliorated CHOP-induced alterations without diminishing CHOP's antineoplastic action. These results indicated that carnosine may ameliorate reproductive disorders induced by CHOP.

Neuromodulatory effect of curcumin on catecholamine systems and inflammatory cytokines in ovariectomized female rats.

Anti-inflammatory products may represent the future for depressive disorder therapies. Curcumin (CUR) is a polyphenol and an active component of the turmeric plant Curcuma longa. The aim of this study was to investigate the impact of CUR, as a natural anti-inflammatory agent, on neuro-inflammation related to depression and compare it with the effects of fluoxetine (FLX) and estradiol (E2 ) in ovariectomized (OVX) rats. The experimental animals were divided into the following five treatment groups (n = 10): sham-operated, OVX, OVX-E2 (100 µg/kg, im, every other day), OVX-FLX (20 mg/kg, ip, daily), and OVX-CUR (100 mg/kg, po, daily). The results indicated that CUR improved the animals' performances in the open field test and modulated dopamine (DA) and norepinephrine levels in several brain regions compared with the OVX group. CUR resulted in the down-regulation of monoamine oxidase b and up-regulation of tyrosine hydroxylase, as well asDA receptor mRNA in the limbic region. In addition, CUR significantly attenuated the production of serum corticosterone hormone, tumour necrosis factor-alpha, interleukin-ß1, interleukin-6, and nitric oxide in the limbic system. Furthermore, CUR normalized malondialdehyde levels and led to a significant upsurge in total antioxidant capacity, compared with the OVX group. Consequently, CUR, besides being harmless, was efficient against inflammation and oxidative-nitrosative stress, showing a greater effect on DA receptor expression than FLX and E2 in OVX rats.

Involvement of the serotonergic system and neuroplasticity in the antidepressant effect of curcumin in ovariectomized rats: Comparison with oestradiol and fluoxetine.

Antidepressant drugs are associated with many challenges due to their adverse impacts. Seeking alternatives through medicinal plants could have a great merit in overcoming these deleterious effects. This study was designed to investigate the potential mechanism of curcumin (CUR) in modifying the depression-like behaviour in ovariectomised (OVX) rats, inference with fluoxetine (FLX) and oestradiol (E2 ). The treatments of OVX rats started after 1 month post ovariectomy and proceeded for 1 month. The experimental animals were divided into five groups: sham-operated, OVX-, OVX-FLX (20 mg kg-1 , i.p., daily), OVX-E2 (100 µg kg-1 , i.m., every other day), and OVX-CUR- (100 mg kg-1 , p.o., daily) treated groups. The results showed that CUR modulated the depression-like behaviour using forced swimming test. It improved the serotonin content in many brain regions by upregulating tryptophan hydroxylase-2 and 5-hydroxytryptamine1A,2A receptor messenger RNA (mRNA) and downregulating monoamine oxidase A mRNA in the limbic system. Furthermore, it upregulated aromatase, brain-derived neurotropic factor mRNA, and extracellular-regulated kinase 1/2 protein in the limbic system, relative to FLX and E2, compared with OVX group. In conclusion, CUR appears to be safe and efficient agent as serotonin modulator similar to FLX and neurotrophic agent like E2 , in improving the depression-like behaviour in OVX rats.

In vivo ameliorative effect of cerium oxide nanoparticles in isoproterenol-induced cardiac toxicity.

BACKGROUND: Cerium oxide nanoparticles have gained much more attention especially in the field of nanomedicine. This work represents cerium oxide nanoparticles as a new prophylactic model for heart failure progression. OBJECTIVE: To investigate the potential protective effect of cerium oxide nanoparticles on Isoproterenol (ISO)-induced cardiac toxicity in rats. METHODS: Cerium oxide nanoparticles (5±1nm) were synthesized by reverse micelle method and characterized using High Resolution Transmission Electron Microscopy, X-Ray Diffraction and particle size analyzer. The experiments were performed on 96 male Wistar rats. The rats were randomly allocated into eight groups. Namely; two Negative and positive control groups, captopril administered group, Nano-ceria (low dose) group, Nano-ceria (high dose) group, Captopril- Isoproterenol group, Nano-ceria (low dose)-Isoproterenol group and Nano-ceria (high dose)-Isoproterenol group. Cardio toxic rat model was induced by subcutaneous administration of Isoproterenol (ISO) (30mg/kg) for two consecutive days in adult male rats. Two doses (0.5 and 5µg/kg/week) of cerium oxide nanoparticles were applied for five weeks and 50mg/kg/day of Captopril was used as a reference drug. Cardiac marker enzymes, Cortisol and Aldosterone hormones were assessed in serum. Oxidant-antioxidant parameters and histopathological examination in heart tissues were also determined. RESULTS: These dose of nano-ceria, showed a promising ameliorative and prophylactic effect against cardiac toxicity compared to Captopril reference drug. Serum cardiac markers were decreased by noticeable percentage, CK-MB (50% and 57%), LDH (47% and 57.7%), AST (38% and 36.5%) and ALT (33.5% and 30.6%) for both doses respectively, while increased tissues level of the antioxidant enzymes, catalase (48% - 26%) and superoxide dismutase (64%, 143%). CONCLUSION: These consistent biochemical and histopathological results suggest that, nano-ceria could be used as effective antioxidant in prophylactic protocols for management of cardiac disorders associated with oxidative stress.