Perindopril Erbumine

Amikacin (AMC), an aminoglycoside antibiotic known for its rapid and potent bactericidal activity, is also associated with nephrotoxicity. Diosmin and perindopril have been reported to improve renal function and hold promise as therapeutic agents for preventing drug-induced nephrotoxicity. This study aimed to investigate the protective effect of Diosmin and perindopril, either alone or in combination, against renal damage induced by AMC toxicity and to elucidate the underlying mechanisms.

The researchers evaluated the impact of Diosmin (50 mg/kg, orally) and perindopril (2 mg/kg, intraperitoneally) on AMC-induced kidney injury (1.2 g/kg, intraperitoneally) in rats. Invasive blood pressure, serum kidney function and toxicity parameters, oxidative stress biomarkers, and inflammatory cytokine levels in serum and renal tissue were assessed. Histopathological changes in the kidney were examined using hematoxylin and eosin (H&E) staining, electron microscopy, and immunohistochemical analysis. The molecular mechanisms underlying the protective effect of the combination pretreatment on kidney injury were investigated using enzyme-linked immunosorbent assay (ELISA) and Western blotting techniques.

The findings demonstrated that the combination therapy improved kidney function by attenuating pathological changes observed in H&E staining including tubular necrosis and glomerular damage, in addition to reducing levels of kidney function including serum levels of creatinine compared to the AMC group, blood urea nitrogen (BUN) uric acid, and albumin. Mean arterial blood pressure, and toxicity markers including Kidney Injury Molecule-1 (KIM-1), Cystatin-c were also decreased in samples of combination group compared to AMC group. Furthermore, the protective combination therapy downregulated NF-κB-p65, P53, Keap-1, and C-FOS, while upregulating Mammalian sirtuin 1 (SIRT1), inhibitor of nuclear factor kappa B (Iκβ), nuclear factor erythroid 2-related factor 2 (Nrf2), and Heme oxygenase-1 (HO-1) levels.

The findings reveal the potential clinical application of combining Diosmin and perindopril to reduce AMC-induced nephrotoxicity, which requires further research in clinical settings.

A 36-year-old man with known history of relapsing multiple sclerosis of 13-year duration who was undergoing continuous treatment with subcutaneous interferon-β (44 µg three times per week) presented to the emergency department of our hospital with blurry vision of 1-week duration. Routine MRI performed 1 month earlier had revealed five new fluid-attenuated inversion recovery (or FLAIR) T2-hyperintense cerebellar lesions without contrast enhancement, suggesting active relapsing multiple sclerosis ( Fig 1 ), albeit without corresponding neurologic deficits. The patient denied any other symptoms, apart from known yet intensified intermittent tension-type headaches. His history was unremarkable for drug use, recent infections, or travel. There was no routine use of other medication. Apart from a markedly elevated blood pressure (214/122 mm Hg), vital signs were within normal ranges (heart rate, 72 beats per minute; temperature, 97.9 °F [36.6 °C]; respiratory rate, 19 breaths per minute; oxygen saturation, 100%). Physical examination findings were unremarkable. Findings of a neurologic examination were normal, except for known saccadic gaze, with an Expanded Disability Status Scale (or EDSS) of 1. Acute ophthalmologic evaluation with fundoscopy showed bilateral hypertensive retinopathy, without signs of optic neuritis. Laboratory analysis revealed known increased liver enzyme levels due to interferon-β treatment (aspartate aminotransferase level, 123 U/L [2.05 µkat/L]; normal range, 11–34 U/L [0.18–0.57 µkat/L]; alanine aminotransferase level, 179 U/L [2.99 µkat/L]; normal range, 9–59 U/L [0.15–0.99 µkat/L]; γ-glutamyl transferase level, 154 U/L [2.57 µkat/L]; normal range, 12–68 U/L [0.20–1.14 µkat/L]). The patient was admitted for further diagnostic evaluation, including new brain ( Figs 2 , 3 ) and spinal (not shown) MRI studies. Antihypertensive treatment with perindopril and amlodipine was initiated. Further laboratory examinations revealed microalbuminuria (albumin-to-creatinine ratio in urine, 59.21 mg/mmol; reference range, <3.00 mg/mmol) and hyperlipidemia (low-density lipoprotein cholesterol level, 3.84 mmol/L; reference range, 1.60–3.40 mmol/L). Blood serologic examination and cerebrospinal fluid laboratory analysis were unremarkable, except for positive oligoclonal bands, with a polymerase chain reaction panel that was negative for common meningitis and/or encephalitis pathogens and a polymerase chain reaction test that was negative for human polyomavirus 2 (or JC virus) DNA in the cerebrospinal fluid. The clinical course supported a wait-and-see approach without the use of steroids or antimicrobial therapy. Follow-up contrast-enhanced brain MRI was performed 1 week after presentation ( Fig 4 ).