RESUMO
Hecogenin (HEC) is a steroidal saponin found in many plant species and serves as a precursor for steroidal drugs. The diuretic effects of HEC and its derivative, hecogenin acetate (HA), remain largely unexplored. The present study aimed to explore the potential diuretic effects of HEC and HA compared to furosemide (FUR) and spironolactone (SPIR). Additionally, the study aimed to explore the underlying mechanism particularly focusing on aldosterone synthase gene expression. Fifty-four Sprague-Dawley rats were allocated into nine groups (Group 1-9). Group 1 (control) received the vehicle, Groups 2 received FUR 10 mg/kg, Group 3, 4, and 5 were given HEC, while Groups 6, 7 and 8 received HA i.p at doses of 5, 10, and 25 mg/kg, respectively. Group 9 received SPIR i.p at the dose of 25 mg/kg. Urine volume, diuretic index and diuretic activity were monitored at 1, 2, 3, 4, 5, 6, and 24 h post-administration. Treatment was given daily for seven days. After that, rats were sacrificed and blood was collected for serum electrolytes determination. Adrenal glands were dissected out for gene expression studies. The results revealed that HEC and HA at the administered doses significantly and dose-dependently increased urine and electrolyte excretion. These results were primarily observed at 25 mg/kg of each compound. Gene expression studies demonstrated a dose-dependent reduction in aldosterone synthase gene expression, suggesting aldosterone synthesis inhibition as a potential mechanism for their diuretic activity. Notably, HA exhibited more pronounced diuretic effects surpassing those of HEC. This enhanced diuretic activity of HA can be attributed to its stronger impact on aldosterone synthase inhibition. These findings offer valuable insights into the diuretic effects of both HEC and HA along with their underlying molecular mechanisms.
RESUMO
Breast cancer patients use numerous medications, which include cytotoxic chemotherapy drugs, hormonal agents and supportive medication, so they are more vulnerable to potential adverse drug interactions. This study aimed to evaluate frequency, severity, clinical importance and risk factors responsible for the Drug-drug interactions (DDIs) in a cohort of patients suffering from breast cancer. Data was obtained from 150 patients in the oncology ward (both inpatient and outpatient) with a confirmed diagnosis of breast cancer and currently receiving standard breast cancer-directed treatment. The data was recorded into a pre-designed form specifically made for this study through individual patient interviews and by reviewing the detailed medical chart records of the patients. DDIs were identified by using drug interaction software such as Medscape mobile application and Micromedex version 2.The results of this study showed that all patients were female. The mean numbers of drugs that patients used were 7. Potential drug interactions were identified in 92% of the patients. When drug groups were overviewed, 32% of interactions were between anti neoplastic drugs, 62.9% interactions were between the anti neoplastic agent and supportive care drugs and 5% of them were between anti-cancer drugs and drugs used to treat comorbidities. Major DDIs were found in 62.2% of patients, 25.3% of DDIs were moderate and 12.4% were minor. The number of drugs, comorbid diseases, and selection of chemo protocols were the risk factors for drug interactions. Most of the DDIs found in breast cancer therapy may have adverse consequences on patient health and therapeutic outcomes. Therefore, health care professionals should review the medication regimen of patients with breast cancer before starting any chemotherapy treatment.