A new approach of nano-metformin as a protector against radiation-induced cardiac fibrosis and inflammation via CXCL1/TGF-Β pathway.

The present work investigates the potential role of metformin nanoparticles (MTF-NPs) as a radio-protector against cardiac fibrosis and inflammation induced by gamma radiation via CXCL1/TGF-ß pathway. Lethal dose fifty of nano-metformin was determined in mice, then 21 rats (male albino) were equally divided into three groups: normal control (G1), irradiated control (G2), and MTF-NPs + IRR (G3). The possible protective effect of MTF-NPs is illustrated via decreasing cardiac contents of troponin, C-X-C motif Ligand 1 (CXCL1), tumor growth factor ß (TGF-ß), protein kinase B (AKT), and nuclear factor-κB (NF-κB). Also, the positive effect of MTF-NPs on insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) in heart tissues using immunohistochemical technique is illustrated in the present study. Histopathological examination emphasizes the biochemical findings. The current investigation suggests that MTF-NPs might be considered as a potent novel treatment for the management of cardiac fibrosis and inflammation in patients who receive radiotherapy or workers who may be exposed to gamma radiation.

A novel approach of using Maca root as a radioprotector in a rat testicular damage model focusing on GRP78/CHOP/Caspase-3 pathway.

PURPOSE: Despite the effectiveness of ionizing radiation in treating cancer, it can damage healthy tissues in the vicinity. Due to the high radio-sensitivity of testicular tissues, radiation therapy may affect spermatogenesis, which may result in infertility. Hence, in this study testicular damage model is constructed to investigate the mitigation effect of Maca root powder and its potential radioprotective activity through both oxidative and endoplasmic reticulum (ER) stresses, besides the apoptotic pathway. METHODS: Male albino rats were exposed to 6Gy of whole-body gamma radiation single dose. Maca root powder (1 g/kg b.wt./day, by oral gavage) was administered for a week before irradiation, then d-galactose (300 mg/kg, by oral gavage) and Maca daily for another week. RESULTS: Gamma radiation and d-galactose revealed a significant decrease in serum testosterone, sperm count, and motility and higher percentage of the sperm head abnormality, while Maca root treatment maintained all sperm morphology parameters. Maca root treatment demonstrated a notable defense against radiation-induced oxidative stress and ameliorated malonaldehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), glutathione-S-transferase (GST) levels, reduced glutathione (GSH), oxidized glutathione (GSSG) and the ratio of GSH/GSSG in testis tissues. Exposure to gamma rays and d-galactose displayed a significant elevation in GRP78, CHOP, total caspase-3 as well as active (cleaved) caspase-3 levels, whereas treatment with Maca significantly reduced the ER and apoptotic markers levels. Also, Maca improved the histological changes of the disorganized seminiferous tubules induced by irradiation. CONCLUSION: Our findings show for the first time that Maca has a protective effect on male reproductive damage induced by radiotherapy. Maca root reveals anti-apoptotic effect and protection against testicular damage via GRP78/CHOP/caspase-3 pathway.

Low dose gamma irradiation attenuates cyclophosphamide-induced cardiotoxicity in rats: role of NF-κB signaling pathway.

PURPOSE: Cyclophosphamide (Cyp) is one of the most commonly used, wide spectrum chemotherapeutic agents. Cyp has multi-organ toxicities that are dose limiting, thus it's mostly used in chemotherapeutic combinations. Radiation is well known as a hazardous sort of energy, recent studies are interested in studying the beneficial therapeutic effects of low-dose gamma radiation. This study examined the protective effect of two different doses/dose-rates of irradiation either alone or combined with telmisartan against Cyp-induced cardiotoxicity. MATERIALS AND METHODS: Rats were divided into seven groups; (1): Control, (2): Cyp, (3-4): 0.05 Gy low dose rate (LDR) irradiation, 0.25 Gy high dose rate (HDR) irradiation, respectively, prior to Cyp dose, (5-7): telmisartan either alone or with 0.05 Gy LDR-irradiation or 0.25 Gy HDR-irradiation, respectively, prior to Cyp dose. The current investigation studied the effect of Cyp alone or combined with different treatment regimens on serum cTn-I and LDH, nuclear factor-κB (NF-κB) pathway (p65/IκB/IKK-α/IKK-ß) in the myocardium. Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were assessed in addition to histopathological examination of the heart. RESULTS: Low-dose irradiation attenuated cardiac enzymes, pro-inflammatory cytokines, NF-κB content, and histology, in both low and HDRs. Furthermore, the combination of low-dose irradiation with telmisartan (an angiotensin-II receptor type-1 blocker and a known cardio-protective drug) offered the best histological results. CONCLUSIONS: Low-dose irradiation-induced amelioration is partially but not completely through canonical activation of NF-κB, and may have another atypical pathway. While telmisartan probably ameliorates NF-κB totally through canonical pathway.

Fractional CO2 Laser for Transcutaneous Drug Delivery of Onabotulinum Toxin in Palmar Hyperhidrosis.

BACKGROUND: Palmar hyperhidrosis is a common disorder of excessive sweating due to over-stimulation of cholinergic receptors on eccrine glands. OBJECTIVE: To compare the efficacy of laser-assisted drug delivery of onabotulinum toxin A (BoNTA) and intradermal BoNTA injections in the management of palmar hyperhidrosis. PATIENTS AND METHODS: This intrapatient comparative study was conducted on 30 adult patients with idiopathic palmar hyperhidrosis. The palms of the patients were divided into 2 groups. Group 1 was treated with intradermal injections of 50 units of BoNTA, whereas Group 2 was subjected to laser-assisted transcutaneous BoNTA delivery using fractional CO2 laser at different doses (25, 50, and 75 units). Each treatment modality was evaluated using the iodine starch test, hyperhidrosis disease severity scale, and gravimetric scoring. RESULTS: Delivery of 75 units of BoNTA to the dermis on the right-sided palms assisted by fractional CO2 laser was clinically equivalent to 50 units of injection on the left side. Pain intensity was significantly higher on the injected side than on the other side. CONCLUSION: Laser-assisted drug delivery of botulinum toxin can be considered an effective and safe alternative for treatment of palmar hyperhidrosis with minimal side effects and complications.