The Relationship With Mad Honey Containing Grayanotoxin and Ovary Tissue

The Relationship Between Oxidative Stress and Apoptosis of Histopathological Changes Made by Mad Honey Containing Grayanotoxin in the Ovary

For our working group, eighteen healthy Sprague-Dawley female rats were recruited and separated into three groups in an experimental animal laboratory.

Group 1 was given mad honey (n:6) (80 mg/kg); Group 2 was given normal honey (n:6) (80 mg/kg), and Group 3 was the control group (n:6). The groups were given normal and mad honey by oral gavage for 30 days in this study. Rats were anesthetized intramuscularly with 50 mg/kg ketamine and 5 mg/kg xylazine on the 30th day of the study. At the conclusion of the study, female rats in the proestrus phase of the estrous cycle (as indicated by vaginal smear) were sacrificed and their ovarian tissues were placed in neutral formalin solution.

Study Overview

• Status: Completed
• Conditions: Ovary Disease
• Intervention / Treatment: Dietary supplement: Mad Honey; Dietary supplement: Normal Honey; Dietary supplement: Control

Detailed Description

Honey poisoning is caused by consuming honey produced by bees that feed on Rhododendron family plants. Rhododendron poisoning goes by names such as mad honey poisoning or grayanotoxin poisoning. The purpose of this study is to determine the effects of grayanotoxin in mad honey on ovarian tissue folliculogenesis in terms of cell death and nitric oxide expression. Three groups of 18 female Sprague-Dawley rats were formed. The first group received mad honey (80 mg/kg), the second group received normal honey (80 mg/kg), and the third group is control. The first and second groups received normal and mad honey by oral gavage for 30 days before being sacrificed under anesthesia The caspase 3 immunostaining group observed a moderate to a strong response, particularly in the granulosa cells of the Graaf follicles in the mad honey group, while the normal honey and control groups observed a weak to moderate reaction. In the mad honey group, immunostaining for caspase8 and caspase 9 revealed a moderate immunoreaction in the granulosa cells of the Graaf follicles, while expression was weak in the normal honey and control groups. The TUNEL approach revealed that the majority of Graaf follicles that exhibited TUNEL positive in the mad honey group and progressed to atresia were Graaf follicles. The iNOS immunoreaction revealed a high level of expression in the mad honey group, particularly in several Graaf follicles. In all three groups, a weak reactivity to eNOS immunostaining was seen in both Graaf follicles and theca external layers. According to the findings of apoptotic and nitric oxide marker expression, it was determined that mad honey may result in an increase in follicular atresia in ovarian follicles when compared to normal honey and control groups.

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• Turkey
  • Mani̇sa
    • Yunusemre, Mani̇sa, Turkey, 45030
      • Hayrunnisa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

experimental animals ( Sprague Dawley rats)

Description

Inclusion Criteria:

• healthy rats

Exclusion Criteria:

• patient rats
• not eating rats

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1: Mad honey	Dietary supplement: Mad Honey; mad honey (80 mg/kg); (n:6)
Group 2: Normal honey	Dietary supplement: Normal Honey; normal honey (80 mg/kg),(n:6)
Group 3: without intervention	Dietary supplement: Control; Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the Mad Honey and Normal Honey findings of the ovary tissue specimens	Analyses of the relationship between oxidative stress and apoptosis of histopathological changes made by mad honey containing grayanotoxin in the ovary	Baseline

Collaborators and Investigators

• Sponsor: Celal Bayar University
• Investigators: Study Chair: Gulsen Gurgen, Manisa Celal Bayar University; Study Chair: Suha Turkmen, Karadeniz Teknik University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Actual): December 15, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Grayonotoxin; Mad Honey; Normal honey; ovary
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Adnexal Diseases; Gonadal Disorders; Ovarian Diseases
• Other Study ID Numbers: MCBU_Madhoney

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No