Toxicological Assessment of Venlafaxine: Acute and Subchronic Toxicity Study in Rats

Abstract

Antidepressants are the most commonly prescribed drugs for psychiatric treatment, and venlafaxine (VEN) is one of the most popular options. Venlafaxine is a nontricyclic dual-acting serotonin-norepinephrine reuptake inhibitor. Although an increased incidence of acute toxicity and addiction has been reported, controlled studies examining its toxic effects on different organs are still lacking. This study investigated the possible toxic effects of VEN on the liver, kidney, and gastric tissues. Three groups of rats were administered saline, a single LD dose (350 mg/kg), or 100 mg/kg VEN daily, followed by increases in the dose of 50 mg/kg every 10 days for 30 days (about 10 times the therapeutic doses). The following parameters of liver and kidney injury were then assayed: alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, prothrombin time, partial thromboplastin time, blood urea nitrogen, and serum creatinine. A histopathological examination was then conducted. Both acute and subchronic administration of VEN produced multiple clinical manifestations in the experimental animals, including seizures, coma, and even death. Moreover, the liver and renal function tests indicated injury in these tissues. Furthermore, the histopathological examination showed signs of organ toxicity after both acute and chronic VEN exposure. This study has shown that VEN has harmful effects on the liver, kidney, and stomach in either a single high dose (LD) or repeated exposure to 10 times the therapeutic doses. As a result, strategies to increase awareness of these effects among physicians and the public are needed because this drug may be addictive.

Lactational exposure to venlafaxine provokes late repercussions on reproductive parameters in male rat offspring

“…Lactational exposure to VEN did not alter testosterone levels or the weight of hormone‐dependent organs such as testis, epididymis and prostate; however, it increased the weight of the vas deferens and kidneys. A study observed significant renal changes in adult rats after treatment with VEN (Paulis et al, 2018). Another research group studied the impacts of the exposure to Fluoxetine (a SSRI) during gestation in rats and found adverse effects on offspring kidney development (Ghavamabadi et al, 2018).…”

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

“…According to various authors, venlafaxine should be recommended for use in primary care as a second-line option following the treatment with selective serotonin reuptake inhibitors (Thase et al, 2017;Schueler et al, 2011). Similar to other antidepressants, venlafaxine has manifested a number of moderate collateral symptoms such as fatigue, nausea, somnolence, or mild gastrointestinal problems; however, eventually, the drug can lead to more serious problems, which include severe lactic acidosis, interstitial pneumonitis, neuropathy, different forms of adult and prenatal cardiomyopathy, as well as liver and kidney affections (Paulis et al, 2018;Ko et al, 2018).…”

A presença de fármacos e cafeína em água superficial e destinada ao consumo humano

“…Ela gera, inclusive, efeitos prejudiciais no fígado, nos rins e no estômago de ratos quando administrada em dose única alta de 350 mg/kg ou exposição repetida a 10 vezes a dose terapêutica (50 mg/kg) (PAULIS et al, 2018).…”