Mesenchymal Stem Cells and/or l-2-oxothiazolidine-4–Carboxylate Improve Hyperlipidemia and Lung Cell Proliferation in Chlorpyrifos-Treated Rats

This study aimed to examine the impact of l-2-oxothiazolidine-4-carboxylate (OTC) or/and bone marrow mesenchymal stem cells (MSCs) on CPF-induced lung toxicity in rats. Male albino rats were divided into six groups. Control: received distilled water; OTC: received OTC (100 mg/kg b.wt./day, oral for one month); CPF (toxicity group) received CPF (17.5 mg/kg b.wt/day, oral for one month; CPF+OTC, CPF group treated with OTC; CPF+MSCs, CPF group treated with MSCs (a single intravenous injection of 2×106cell in PBS and left for one month) and CPF+OTC+MSCs, CPF group co-treated with OTC and MSCs. Results showed significant improvement in body weights, relative lung weights, total protein and albumin, lipid profile, and arterial blood gases (pO2 and (pCO2) levels in rats treated with either OTC alone or with MSCs. OTC or/and MSCs exhibited remarkable anti-inflammatory activities evident by increased interleukin-10 (IL-10) and decreased C-reactive protein (CRP), in lung tissues. Notably, OTC or/and MSCs administration exerted restorative effects on the pulmonary parenchyma structure and associated functional impairments. BM-MSCs and OTC combination has the ability to suppress the CPF-induced lung toxicity and could prove to be a novel approach to therapy for acute and chronic lung injury in rats.

Does Gender Difference Effect Radiation-Induced Lung Toxicity? An Experimental Study by Genetic and Histopathological Predictors

Several studies have reported differences in radiation toxicity between the sexes, but these differences have not been tested with respect to histopathology and genes. This animal study aimed to show an association between histopathological findings of radiation-induced lung toxicity and the genes ATM, SOD2, TGF-β1, XRCC1, XRCC3 and HHR2. In all, 120 animals were randomly divided into 2 control groups (male and female) and experimental groups comprising fifteen rats stratified by sex, radiotherapy (0 Gy vs. 10 Gy), and time to sacrifice (6, 12, and 24 weeks postirradiation). Histopathological evaluations for lung injury, namely, intra-alveolar edema, alveolar neutrophils, intra-alveolar erythrocytes, activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis, and collapse were performed under a light microscope using a grid system; the evaluations were semi quantitatively scored. Then, the alveolar wall thickness was measured. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to determine gene expression differences in ATM, TGF-β1, XRCC1, XRCC3, SOD2 and HHR2L among the groups. Histopathological data showed that radiation-induced acute, subacute, and chronic lung toxicity were worse in male rats. The expression levels of the evaluated genes were significantly higher in females than males in the control group, but this difference was lost over time after radiotherapy. Less toxicity in females may be attributable to the fact that the expression of the evaluated genes was higher in normal lung tissue in females than in males and the changes in gene expression patterns in the postradiotherapy period played a protective role in females. Additional data related to pulmonary function, lung weights, imaging, or outcomes are needed to support this data that is based on histopathology alone.

Evaluation of the Clinical Outcomes of Altered Fractionated Radiotherapy in Node Positive Breast Cancer (A Retrospective Study)

Background Hypofractionated radiotherapy schedules provide alternative shorter courses of radiotherapy of more than 2 Gy per fraction and lower total doses compared to the conventionally fractionated schedule of 1.8–2.0 Gy per fraction in 25 fractions. Hypofractionated radiotherapy offers the advantage of improving patients’ convenience and reducing cost and resource requirements. Aim To evaluate the efficacy and toxicity of hypofractionated radiotherapy compared to the conventional schedule. Methods In this retrospective study, the clinical data of 140 patients of node positive breast cancer patients were analyzed. Radiation toxicities and locoregional recurrence were compared between patients who received conventionally fractionated radiation schedule and those who received hypofractionated radiation schedules. Results After a median follow-up of 48 months, the incidence of loco-regional recurrence was comparable between the conventional and hypofractionated arms; 4% vs 3.1%, respectively (P-value = 0.769). Documented acute skin toxicity with ≥ grade 3 was found in 10.6% of the conventional group and in 5.6% of the hypofractionated group (p = 0.409). Grade 1 late lung toxicity was manifested in 6.1% of the conventional group and 7.5% of the hypofractionated group and G2 lung toxicity was found in one case only (1.9%) in the hypofractionated group (p = 0.596). Cardiac toxicity was documented in five cases; 9.4% and 5.1% in the conventional group and hypofractionated groups, respectively (pvalue=0.486). Conclusion Hypofractionated radiotherapy is comparable to conventional radiotherapy regarding locoregional tumor control and treatment toxicities.

Evaluation of Oxidative Stress, Inflammation, Apoptosis, Oxidative DNA Damage and Metalloproteinases in the Lungs of Rats Treated With Cadmium and Carvacrol

Background: The potential protective properties of carvacrol (CRV), which possesses various biological and pharmacological properties, against lung toxicity caused by cadmium (Cd), a major environmental pollutant, were investigated in the present study. Methods and Results: In the study, rats were given 25 or 50 mg/kg CRV orally 30 minutes after administrating 25 mg/kg cadmium chloride for seven days. Subsequently, the levels of 8-OHdG, MMP-2, and MMP-9, as well as markers of oxidative stress, inflammation, and apoptosis, were analyzed in the lung tissue of the animals. The results revealed that CRV exhibited antioxidant characteristics and raised SOD, CAT, GPx, and CAT levels and decreased the MDA levels induced by Cd. It also suppressed proinflammatory cytokines by lowering the levels of CRV NF-kB and p38 MAPK, thus exerting an anti-inflammatory effect against Cd. It was found that the levels of Bax, Caspase-3, and cytochrome c increased by Cd were decreased by the application of CRV. CRV also showed an anti-apoptotic effect by increasing Bcl-2 levels. The levels of 8-OHdG, MMP2, and MMP9, which increased with Cd administration, were observed to reduce after treatment with CRV. Conclusions: The results show that CRV has protective properties against Cd-induced lung toxicity.