Diosmin

Immune checkpoint inhibitors (ICIs) play a central role in cancer immunotherapy. However, the occurrence of immune-related adverse events, especially ICI-induced interstitial lung disease (ICI-ILD), is life-threatening and affects the effectiveness of ICI treatment. This study aimed to explore potential drugs to mitigate ICI-ILD occurrence using data from the Japanese Adverse Drug Event Report (JADER) and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS [JAPIC AERS]).

We investigated concomitant drugs that reduce ILD associated with four ICIs - nivolumab, pembrolizumab, atezolizumab, and durvalumab - across the JADER and FAERS databases. Subsequently, the identified common concomitant drugs that reduce the occurrence of ICI-ILD were detected and analyzed.

We found omega-3 fatty acids, loperamide, and amlodipine as common concomitant drugs that reduced ICI-ILD occurrence in both the JADER and FAERS databases. Omega-3 fatty acids reportedly have many effects in animal models of drug-induced ILD, including their association with ILD in humans and anti-inflammatory effects against ICI-ILD. However, loperamide and amlodipine reportedly have minimal effects against ILD, thereby necessitating further evaluation.

Omega-3 fatty acids have emerged as potential agents for reducing ICI-ILD occurrence, as evidenced by findings from two different pharmacovigilance databases.

Cyclophosphamide (CYC) is a well-established nephrotoxic agent widely used in the treatment of cancer and various immunosuppressive disorders. Diosmin, a bioactive flavonoid, has been reported to reduce drug-induced adverse effects. This study evaluates the effects of diosmin on CYC-induced nephrotoxicity and explores potential mechanisms involved in CYC-related renal damage. Thirty-two male rats were randomly assigned to four experimental groups: control, diosmin, CYC, and CYC + diosmin. Diosmin (100 mg/kg) was administered once daily for 15 consecutive days, while cyclophosphamide (200 mg/kg) was given as a single dose on the 8th day of the experimental period. Diosmin was associated with attenuation of CYC-induced pathological alterations in renal tissue architecture. It reduced the immunoreactivity of pro-inflammatory mediators (IL-1β, IL-6, TNF-α, and iNOS) and modulated apoptosis by decreasing the pro-apoptotic marker BAX and increasing the anti-apoptotic marker Bcl-2. Although CYC treatment suppressed mTOR and increased SIRT1 immunoreactivity, diosmin co-administration attenuated these alterations. Additionally, markers of renal DNA damage were reduced. Overall, the findings suggest that diosmin may exert favorable effects in CYC-induced nephrotoxicity in this experimental model.