THE EFFECT OF NEROLIDOL ON THE RENAL DYSFUNCTION FOLLOWING BILATERAL URETERAL OBSTRUCTION IN THE RAT
Date of Defense
11-11-2024 1:00 PM
Location
YANAH Theatre
Document Type
Thesis Defense
College
College of Medicine and Health Sciences
Department
Surgery
First Advisor
Prof. Fayez Tawfig Fayez Hammad
Abstract
This thesis addressed nerolidol’s potential therapeutic and protective effects on bilateral ureteral obstruction-induced uropathy in rats. Obstructive uropathy stands as a notable contributor to acute kidney injury (AKI), accounting for 5-10% of all AKI cases worldwide, with a particularly high prevalence among the elderly, constituting 22% of AKI cases in this age group. Urinary tract obstruction, often attributed to factors such as kidney stones, urinary tract deformities and benign/malignant growths such as benign prostatic hyperplasia (BPH) in older men can lead to detrimental outcomes if left untreated, potentially progressing to kidney failure and even mortality. The severity of the kidney injury is contingent upon the nature and duration of the obstruction. Common treatment approaches include surgical intervention to remove the obstruction and the subsequent monitoring of the serum chemistry of the patient to address any post-obstruction complications that could lead to alterations in kidney function and prescribing the appropriate medications. Recently, there has been a burgeoning interest in exploring natural products that are seen as a potential alternative remedy for many diseases and conditions. This is due to their low toxicity, affordability, and wide availability, which underscores the need for comprehensive research to address the therapeutic potential of these natural products. Nerolidol, which is a naturally occurring sesquiterpene alcohol compound found in the essential oils of many plants, is believed to exhibit a wide range of pharmacological and biological activities, making it a hot topic of clinical research. Although nerolidol has exhibited effectiveness in various organ-related conditions, as reported by several research studies, its effects on renal dysfunction following reversible bilateral ureteral obstruction (BUO) remain unexplored. Hence, the primary objective of this research was to investigate the in-vivo effects of nerolidol on the alterations in renal function associated with BUO in the rat. Nerolidol was administered orally to Wistar rats using an oral gavage needle after being dissolved in corn oil which was used as a vehicle. Nerolidol was administered as a single daily dose of 200 mg/Kg for 14 consecutive days. Sham group (n=12) underwent sham surgery, whereas the BUO group (n=12) and BUO/NERO group (n=12) underwent reversible 24-hour BUO and received the vehicle or Nerolidol, respectively. The treatment started 9 days prior to the BUO/Sham surgery and continued till 4 days post-BUO. Renal functional parameters and histological changes were assessed before the start of the treatment (Basal), just prior to the intervention (BUO/Sham surgery) (Pre-BUO) and 4 days after the intervention (Post-BUO). The gene and protein expression levels of some important markers of renal injury, inflammation, fibrosis, apoptosis, autophagy, and oxidative stress were measured using PCR and western blot techniques. Neither nerolidol nor the vehicle affected the basal renal functions. The administration of nerolidol resulted in a significant attenuation in the BUO-induced alterations in renal functional parameters such as serum creatinine and serum urea, creatinine clearance and urinary albumin-creatinine ratio. Nerolidol also exhibited the ability to attenuate the changes in several markers associated with renal injury, inflammation, fibrosis, autophagy, and oxidative stress. Moreover, nerolidol was able to attenuate the BUO-induced alterations in kidney histology. The study's findings may provide insights into the potential therapeutic and reno-protective effects of nerolidol on obstructive uropathy-induced kidney injury that could be extended to the clinical setting.
Included in
THE EFFECT OF NEROLIDOL ON THE RENAL DYSFUNCTION FOLLOWING BILATERAL URETERAL OBSTRUCTION IN THE RAT
YANAH Theatre
This thesis addressed nerolidol’s potential therapeutic and protective effects on bilateral ureteral obstruction-induced uropathy in rats. Obstructive uropathy stands as a notable contributor to acute kidney injury (AKI), accounting for 5-10% of all AKI cases worldwide, with a particularly high prevalence among the elderly, constituting 22% of AKI cases in this age group. Urinary tract obstruction, often attributed to factors such as kidney stones, urinary tract deformities and benign/malignant growths such as benign prostatic hyperplasia (BPH) in older men can lead to detrimental outcomes if left untreated, potentially progressing to kidney failure and even mortality. The severity of the kidney injury is contingent upon the nature and duration of the obstruction. Common treatment approaches include surgical intervention to remove the obstruction and the subsequent monitoring of the serum chemistry of the patient to address any post-obstruction complications that could lead to alterations in kidney function and prescribing the appropriate medications. Recently, there has been a burgeoning interest in exploring natural products that are seen as a potential alternative remedy for many diseases and conditions. This is due to their low toxicity, affordability, and wide availability, which underscores the need for comprehensive research to address the therapeutic potential of these natural products. Nerolidol, which is a naturally occurring sesquiterpene alcohol compound found in the essential oils of many plants, is believed to exhibit a wide range of pharmacological and biological activities, making it a hot topic of clinical research. Although nerolidol has exhibited effectiveness in various organ-related conditions, as reported by several research studies, its effects on renal dysfunction following reversible bilateral ureteral obstruction (BUO) remain unexplored. Hence, the primary objective of this research was to investigate the in-vivo effects of nerolidol on the alterations in renal function associated with BUO in the rat. Nerolidol was administered orally to Wistar rats using an oral gavage needle after being dissolved in corn oil which was used as a vehicle. Nerolidol was administered as a single daily dose of 200 mg/Kg for 14 consecutive days. Sham group (n=12) underwent sham surgery, whereas the BUO group (n=12) and BUO/NERO group (n=12) underwent reversible 24-hour BUO and received the vehicle or Nerolidol, respectively. The treatment started 9 days prior to the BUO/Sham surgery and continued till 4 days post-BUO. Renal functional parameters and histological changes were assessed before the start of the treatment (Basal), just prior to the intervention (BUO/Sham surgery) (Pre-BUO) and 4 days after the intervention (Post-BUO). The gene and protein expression levels of some important markers of renal injury, inflammation, fibrosis, apoptosis, autophagy, and oxidative stress were measured using PCR and western blot techniques. Neither nerolidol nor the vehicle affected the basal renal functions. The administration of nerolidol resulted in a significant attenuation in the BUO-induced alterations in renal functional parameters such as serum creatinine and serum urea, creatinine clearance and urinary albumin-creatinine ratio. Nerolidol also exhibited the ability to attenuate the changes in several markers associated with renal injury, inflammation, fibrosis, autophagy, and oxidative stress. Moreover, nerolidol was able to attenuate the BUO-induced alterations in kidney histology. The study's findings may provide insights into the potential therapeutic and reno-protective effects of nerolidol on obstructive uropathy-induced kidney injury that could be extended to the clinical setting.