Protective effects of naringin on colistin‐induced damage in rat testicular tissue: Modulating the levels of Nrf‐2/HO‐1, AKT‐2/FOXO1A, Bax/Bcl2/Caspase‐3, and Beclin‐1/LC3A/LC3B signaling pathways

• Published in: Journal of biochemical and molecular toxicology Vol. 38; no. 2; pp. e23643 - n/a
• Main Authors: Kankılıç, Nazım Abdülkadir, Şimşek, Hasan, Akaras, Nurhan, Gür, Cihan, İleritürk, Mustafa, Küçükler, Sefa, Akarsu, Serkan A., Kandemir, Fatih M.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2024
• Subjects: AKT protein; Animals; Antimicrobial agents; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Apoptosis; Attenuation; Autophagy; BAX protein; Bcl-2 protein; bcl-2-Associated X Protein - metabolism; Beclin-1 - metabolism; Caspase; Caspase 3 - metabolism; Catalase; Colistin; Colistin - adverse effects; Damage assessment; Flavanones; Flavonoids; Glutathione; Glutathione peroxidase; Inflammation; Inflammation - metabolism; Male; Multidrug resistance; naringin; Oxidative Stress; Peroxidase; Proto-Oncogene Proteins c-akt - metabolism; Rats; Semen - metabolism; Signal Transduction; Superoxide dismutase; Testes; testicular toxicity; Testis - metabolism; Tissues; Toxicity; testicular toxicity; apoptosis; naringin; autophagy; colistin; oxidative stress
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.23643

Antimicrobial agent resistance has become a growing health issue across the world. Colistin (COL) is one of the drugs used in the treatment of multidrug‐resistant bacteria resulting in toxic effects. Naringin (NRG), a natural flavonoid, has come to the fore as its antioxidant, anti‐inflammatory, and antiapoptotic activities. The aim of the present study was to determine whether NRG has protective effects on COL‐induced toxicity in testicular tissue. Thirty‐five male Spraque rats were randomly divided into five groups (n = 7 per group): Control, COL, NRG, COL + NRG 50, COL + NRG 100. COL (15 mg/kg b.w., i.p., once per/day), and NRG (50 or 100 mg/kg, oral, b.w./once per/day) were administered for 7 days. The parameters of oxidative stress, inflammation, apoptosis, and autophagic damage were evaluated by using biochemical, molecular, western blot, and histological methods in testicular issues. NRG treatment reversed the increased malondialdehyde level and reduced antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione) levels due to COL administration (p < 0.001), and oxidative stress damage was mitigated. Nuclear factor erythroid 2‐related factor‐2 pathway, one of the antioxidant defence systems, was stimulated by NRG (p < 0.001). NRG treatment reduced the levels of markers for the pathways of apoptotic (p < 0.001) and autophagic (p < 0.001) damages induced by COL. Sperm viability and the live/dead ratio were reduced by COL but enhanced by NRG treatment. Testicular tissue integrity was damaged by COL but showed a tendency to improve by NRG. In conclusion, COL exhibited toxic effect on testicular tissue by elevating the levels of oxidative stress, apoptosis, autophagy, inflammation, and tissue damage. NRG demonstrated a protective effect by alleviating toxic damage. Naringin may attenuate colistin‐induced testicular toxicity by reducing oxidative stress, apoptosis, and endoplasmic reticulum stress. Highlights Colistin induces testicular toxicity. Naringin attenuates colistin‐induced oxidative stress. Naringin attenuates colistin‐induced inflammation. Naringin attenuates colistin‐induced apoptosis. Naringin attenuates colistin‐induced autophagy.