Thesis Summary



TITLE:

          Studies On the Neurotoxicology Of Argemone oil

Subject : Toxicology
Department : Medical Elementology &   Toxicology, Faculty of   Science
Name of the student : ALMAS SIDDIQUI.almassiddiqui@yahoo.com.
Name of the supervisor : Dr. Fakhrul.Islam.fislam2001@yahoo.com.
Source of funding

: Central Council of Research in Unani medicine   (CCRUM)

Date of Viva Voce : 20th December 2002


Summary

Chapter 1 describes the in vivo protection of argemone oil induced neurotoxicity by Argemone mexicana aqueous extract. All the rats were sacrificed and their brain were dissected out for the estimations of Na+ K+ ATPase, lipid peroxidation, reduced glutathione content and the activity of glutathione metabolizing enzymes, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and serum was used for the study of the marker enzymes of hepatotoxicity; serum glutamate pyruvate transaminase (SGPT) & serum glutamate oxaloactate transaminase (SGOT). Argemone oil depleted the content and activity of all the above parameters significantly and increase the activity of SGPT & SGOT. The A. mexicana aqueous extract protected the activity of Na+ K+ ATPase, GPx, GR, GST and content of GSH to a significant level and brings down the activity of SGPT & SGOT and the content lipid peroxide in brain when compared to the group treated with argemone oil alone. These results indicate that prophylactic treatment of A. mexicana aqueous extract offered partial protection against argemone oil induced neurotoxicity and hepatotoxicity.

Chapter 2 describes the in vivo protection of argemone oil induced neuro & hepatotoxicity by argemone maxicana aqueous extract for a period of 15days.. On day 16th all the rats were sacrificed and there brain parts and liver were dissected out for the estimations of lipid peroxidation, reduced glutathione and the activity of glutathione metabolizing enzymes, glutathione peroxidase, glutathione reductase and glutathione S-transferase. The Argemone maxicana aqueous extract was found to be helpful in up regulating the enzymes activity to a significant level and lowering down the lipid peroxidation in brain areas as well as in liver when compared with argemone oil treated group. These results indicate that prophylactic treatment of Argemone mexicana aqueous extract offered partial protection against argemone oil induced toxicity in discrete brain areas and liver.

Chapter 3 describes the in vivo effect of acute and sub acute doses of argemone oil on antioxidant status in striatum, hypothalamus, hippocampus & thalamus. Adult male Wistar rats (125±10 g) from Jamia Hamdard animal breeding colony were used in this study and kept on commercial pellet diet and water ad libitum for 12 hr light and dark cycle each. The animals were divided into four groups two control and two experimental each having 8 rats. Group 1 and 2 received intra peritoneal (i.p) injection of saline for 3 and 15 days respectively which served as control. The group 3 and group 4 received argemone oil 1.5 mL/kg b wt & 0.2 mL/kg b wt through i.p. route for3 and 15 days respectively. On day 16th animals were sacrificed and brain regions were dissected out for estimations of lipid peroxidation, glutathione & its metabolizing enzymes; glutathione peroxidase, glutathione reductase and glutathione-S-transferase. These results suggest that a lower dose of argemone oil when given for longer duration is more toxic as compare to the higher dose which was given for short duration.

Chapter 4 describes the in vivo effect of argemone oil on antioxidant status, dopamine (DA) and its metabolite dihydroxy phenyl acetic acid (DOPAC) in striatum, hypothalamus, hippocampus & thalamus regions of the brain. The SGPT and SGOT were estimated in the serum of the animals. The male albino rats (125±10g) were divided into 4 groups each having 8 animals. The group I received normal saline i.p. for 14 days. Group II, III & IV received argemone oil 0.05, 0.1 and 0.2 ml/kg b.wt (i.p.) respectively for 14 days. On day 15, all the animals were sacrificed and brain regions were dissected out for estimations of DA, DOPAC, lipid peroxidation, glutathione & its metabolizing enzymes; glutathione peroxidase, glutathione reductase and glutathione-S-transferase. It has elevated the level of DA and DOPAC in all the regions significantly and dose dependently. Argemone oil has depleted the level of reduced glutathione and the activity of its dependent enzymes and increase the content of LPO at the dose of 0.1 & 0.2 ml/kg, but no significant changes were observed with 0.05 ml/kg. The argemone oil (0.1 & 0.2 ml/kg) doses has increased the activity of SGPT and SGOT but no significant changes were observed with 0.05 ml/kg argemone oil. Our results suggest that use of argemone oil at lower doses might be of therapeutic importance in the diseases where there is a potential loss of dopamine take place.

CONCLUSIONS
Argemone oil shows its acute and subacute as well as dose dependent toxicity in whole brain as well as in discrete areas of brain; Striatum, hypothalamus, hippocampus and thalamus..Oral supplementation of aqueous extract of A. mexicana stem & leave shows the protective effect on the brain and liver.At lower doses, argemone oil might have some beneficial effect in neurodegenerative disorders like Parkinson's and Huntingtoncorea where there is a severe loss of Dopamine as argemone oil enhances the level of Dopamine and its metabolite DOPAC without any apparent signs of toxicity

"Nature Has Provided Toxicity and Remedy In the Same Plant"