Cisplatin (CIS) is an effective chemotherapeutic agent against different cancers. The use of CIS is associated with acute lung injury (ALI) and other adverse effects, and oxidative stress and inflammation were implicated in its toxic effects. Candesartan (CAN), an angiotensin II (Ang II) receptor blocker, showed beneficial effects against oxidative stress and inflammation. Therefore, this study investigated the potential of CAN to prevent CIS-induced oxidative stress, inflammation, and lung injury in rats, pointing to the involvement of TLR4/NF-κB, JAK1/STAT3, PPARγ, and Nrf2/HO-1 signaling. The rats received CAN (5 mg/kg) for 10 days and were challenged with a single dose of CIS (7 mg/kg) on day 7. CIS caused injury to the alveoli and the bronchial tree, increased lipid peroxidation, nitric oxide, myeloperoxidase, TLR-4, NF-κB p65, iNOS, TNF-α, IL-6, IL-1β, and caspase-3, and decreased cellular antioxidants and IL-6 in the lungs of rats. CAN effectively prevented tissue injury, suppressed TLR-4/ NF-κB signaling, and ameliorated oxidative stress, inflammatory markers, and caspase-3 in CIS-administered rats. CAN enhanced antioxidants and IL-10, decreased Ang II, increased Ang (1–7), suppressed the phosphorylation of JAK1 and STAT3, and upregulated SOCS3 in CIS-administered rats. These effects were associated with the downregulation of Keap1 and enhanced Nrf2, GCLC, HO-1, and PPARγ. In conclusion, CAN prevented CIS-induced lung injury by attenuating oxidative stress, suppressing TLR-4/NF-κB and JAK1/STAT3 signaling, Ang II, and pro-inflammatory mediators, and upregulating PPARγ, and Nrf2/HO-1 signaling.

Acute lung injury (ALI) is one of the adverse effects of the antineoplastic agent cisplatin (CIS). Oxidative stress, inflammation, and necroptosis are linked to the emergence of lung injury in various disorders. This study evaluated the effect of the macrolide antibiotic azithromycin (AZM) on oxidative stress, inflammatory response, and necroptosis in the lungs of CIS-administered rats, pinpointing the involvement of PPARγ, SIRT1, and Nrf2/HO-1 signaling. The rats received AZM for 10 days and a single dose of CIS on the 7th day. CIS provoked bronchial and alveolar injury along with increased levels of ROS, MDA, NO, MPO, NF-κB p65, TNF-α, and IL-1β, and decreased levels of GSH, SOD, GST, and IL-10, denoting oxidative and inflammatory responses. The necroptosis-related proteins RIP1, RIP3, MLKL, and caspase-8 were upregulated in CIS-treated rats. AZM effectively prevented lung tissue injury, ameliorated oxidative stress and NF-κB p65 and pro-inflammatory markers levels, boosted antioxidants and IL-10, and downregulated necroptosis-related proteins in CIS-administered rats. AZM decreased the concentration of Ang II and increased those of Ang (1-7), cytoglobin, PPARγ, SIRT1, Nrf2, and HO-1 in the lungs of CIS-treated rats. In conclusion, AZM attenuated the lung injury provoked by CIS in rats through the suppression of inflammation, oxidative stress, and necroptosis. The protective effect of AZM was associated with the upregulation of Nrf2/HO-1 signaling, cytoglobin, PPARγ, and SIRT1.

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The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine, and its hepatic expression is up-regulated during chronic HCV infection. Fifty naive patients with chronic hepatitis C in National Hepatology & Tropical Medicine Research Institute and 20 healthy volunteers as controls were enrolled in a prospective study designed with strict inclusion criteria to nullify the effect of confounding variables and further minimize selection bias. Fifty naïve patients were treated with PEG-IFN-a2b, at a dose of 180lg/kg subcutaneously every week plus ribavirin at a dose of 1000-1200 mg/day, according to the patient's body weight, for 48 weeks. Quantification of HCV-RNA by real-time PCR and MCP-1 by ELISA were performed for every patient and controls. There was a statistically significant difference between patients and control group as regards the quantity of MCP-1 (P <0.05) (Mann-Whitney test) (P =0.004). There was a significant difference between responders and nonresponses regarding MCP-1 (P < 0.05), responders showed a higher percentage of cases with initial MCP-1< 306 (P < 0.05). We conclude the importance of the detection of MCP-1 expression at the start of therapy as a factor for assessing the likelihood of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN-a2 in combination with ribavirin.