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.

Nazım Abdülkadir Kankılıç, Hasan Şimşek, Nurhan Akaras, Cihan Gür, Mustafa İleritürk, Sefa Küçükler, Serkan A Akarsu, Fatih M Kandemir
Author Information
  1. Nazım Abdülkadir Kankılıç: Department of Urology, Faculty of Medicine, Aksaray University, Aksaray, Turkey. ORCID
  2. Hasan Şimşek: Department of Physiology, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
  3. Nurhan Akaras: Department of Histology and Embryology, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
  4. Cihan Gür: Department of Veterinary Biochemistry, Faculty of Veterinary, Atatürk University, Erzurum, Turkey. ORCID
  5. Mustafa İleritürk: Department of Animal Science, Horasan Vocational College, Atatürk University, Erzurum, Turkey. ORCID
  6. Sefa Küçükler: Department of Veterinary Biochemistry, Faculty of Veterinary, Atatürk University, Erzurum, Turkey.
  7. Serkan A Akarsu: Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey. ORCID
  8. Fatih M Kandemir: Department of Medical Biochemistry, Aksaray University, Aksaray, Turkey.

Abstract

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.

Keywords

References

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MeSH Term

Rats
Male
Animals
Antioxidants
bcl-2-Associated X Protein
Proto-Oncogene Proteins c-akt
Colistin
Beclin-1
Caspase 3
Semen
Oxidative Stress
Testis
Signal Transduction
Inflammation
Apoptosis
Flavanones

Chemicals

Antioxidants
naringin
bcl-2-Associated X Protein
Proto-Oncogene Proteins c-akt
Colistin
Beclin-1
Caspase 3
Flavanones

Word Cloud

Created with Highcharts 10.0.0NRGCOLtesticulardamagetreatmenttissueoxidativestresslevelsp < 0001toxiceffectsapoptosisreducedoneantioxidantprotectivetoxicityCOL + NRGbwper/dayinflammationautophagicglutathionepathwayseffectautophagynaringinAntimicrobialagentresistancebecomegrowinghealthissueacrossworldColistindrugsusedmultidrug-resistantbacteriaresultingNaringinnaturalflavonoidcomeforeanti-inflammatoryantiapoptoticactivitiesaimpresentstudydeterminewhetherCOL-inducedThirty-fivemaleSpraqueratsrandomlydividedfivegroupsn = 7pergroup:Control5010015 mg/kgip50 or100 mg/kgoral/onceadministered7daysparametersevaluatedusingbiochemicalmolecularwesternblothistologicalmethodsissuesreversedincreasedmalondialdehydelevelantioxidantssuperoxidedismutasecatalaseperoxidasedueadministrationmitigatedNuclearfactorerythroid2-relatedfactor-2pathwaydefencesystemsstimulatedmarkersapoptoticdamagesinducedSpermviabilitylive/deadratioenhancedTesticularintegritydamagedshowedtendencyimproveconclusionexhibitedelevatingdemonstratedalleviatingProtectivecolistin-inducedrattissue:ModulatingNrf-2/HO-1AKT-2/FOXO1ABax/Bcl2/Caspase-3Beclin-1/LC3A/LC3Bsignalingcolistin

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