Doxorubicin (DOX) is used in the treatment of cancer. However, cardiotoxicity is its major dose-limiting factor. Mechanism of DOX–cardiac toxicity is not completely elucidated. The aim of the current study was to explore whether the addition of subeffective dose of curcumin (100 mg/kg) to nebivolol would produce a better impact in treating DOX-induced cardiac toxicity in comparison with monotherapy. Male rats were used and subdivided into seven groups. Cardiac toxicity was induced in 6 groups by intraperitoneal injection of DOX over 23 days; of the six groups, five groups were treated with curcumin (100 and 200 mg/kg), nebivolol (1 and 2 mg/kg), and their combination; the sixth group was the control group used for comparison. Oral administration of curcumin and/or nebivolol attenuated DOX cardiotoxicity as manifested by increasing survival rate, improvement in body weight, heart index, and ECG parameters, increase in ventricular isoprenaline responses, and improvement in cardiac enzymes, oxidative stress, apoptosis, and histopathological picture. The addition of the current low subeffective dose of curcumin to nebivolol ameliorated DOX cardiac toxicity to a much greater extent than monotherapy showing better antioxidant and antiapoptotic effects versus the per se effect of nebivolol. Therefore, the current study encourages adding low dose of curcumin to potentiate the effect of nebivolol in the clinical management of cardiac toxicity improving the patients’ quality of life if proper clinical safety data are available.
Aim: The identification and application of stem cells to treat central nervous system disorders represent a dramatic evolution and expansion into the realms of neurorestoration and neuroregeneration. The aim of this study was to assess the possible ameliorative effect of mesenchymal stem cells (MSCs) in comparison to gabapentin on pentylenetetrazole (PTZ)-induced epileptogenesis and its consequences. Methods: Thirty-two rats were divided into 4 equal groups; group I: saline-injected group, group II: PTZ group, which received 13 intraperitoneal (i.p.) injections of PTZ (30 mg/kg) 3 times/week, groups III and IV: groups received PTZ and were treated with i.p. gabapentin (200 mg/kg) 60 min before each PTZ injection (group III) or a single intravenous injection of 106 MSCs/rat at day 22 (group IV). Results: Treatment with either gabapentin or MSCs demonstrated a significant improvement in the PTZ-induced epileptogenesis and its severe consequences, i.e. oxidative stress damage, motor and cognitive impairments. Moreover, they enhanced the GABA neurotransmitter levels. Meanwhile, MSC administration to chronic epileptic rats afforded more ameliorative effects on PTZ-induced epileptogenesis and its severe consequences in comparison to gabapentin. Conclusion: These data indicate that MSCs were superior to gabapentin in ameliorating PTZ-induced epileptogenesis and verified the potential use of MSCs in seizure control, motor and cognitive impairments, oxidative stress, and the impairing GABA level in experimentally induced epilepsy.
The overlapping between asthmatic subtypes, including both CD4+ T helper (TH)2 and TH17 cells, is found in the natural course of allergic asthma, especially in exacerbations and severe and insensitive forms to steroids, which are in need of new molecular therapies. In the TH2-subset mediated asthma, fenofibrate displays therapeutic promises, besides evidenced therapeutic effects on TH17-mediated colitis and myocarditis. Therefore, the effects of fenofibrate versus dexamethasone on IL-23/IL-17 axis in ovalbumin (OVA)/lipopolysaccharide (LPS)-induced airway inflammation and bronchial asthma in rats were explored. The OVA/LPS sensitization and challenge were performed for 28 days in male Wistar rats. After sensitization, fenofibrate (100 mg/kg/day) or dexamethasone (2.5 mg/kg/day) was orally administered from the day 15 to 28. Either fenofibrate or dexamethasone attenuated the severity of OVA/LPS-induced airway inflammation and bronchial asthma through significant ameliorations in the total serum immunoglobulin (Ig)E assay; the total and differential leukocytic counts in the bronchoalveolar lavage (BAL) fluid; the lung inflammatory cytokines such as interleukin (IL)-4, IL-13, IL-17, and IL-23, transforming growth factor (TGF)-β, and tumor necrosis factor(TNF)-α levels; and the lung IL-17 and IL-23 expressions. In addition to the reduction in the inflammatory and fibrotic histopathological scores, fenofibrate significantly ameliorated the BAL neutrophilic count and the lung IL-17 and IL-23 expressions in comparison to dexamethasone. The suppression of IL-23/IL-17 axis could be considered a molecular therapeutic target for fenofibrate in OVA/LPS-induced airway inflammation and bronchial asthma. Combined therapeutic regimens of fenofibrate and steroids should be furtherly investigated in severe and resistant asthma.
In rats with AIA, current drug combinations provided higher therapeutic benefit compared to monotherapies, however, greater toxicities were observed. Therefore, continuous monitoring of hematologic parameters and liver function will be recommended in clinical settings.
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