LYCOPENE EFFICACY TOWARDS STREPTOZOTOCIN INDUCE COGNITIVE DYSFUNCTION: A PRELIMINARY POSSIBLE FUTURE ALTERNATIVE FOR NEUROLOGICAL AILMENTS

still Current emphasizes on Lycopene 100 mg/kg dose positive impressive results against cognitive

Lycopene, a red-colored carotenoid recognized for antioxidant potentials. Being an effective radical scavenger, it owes for various neurological activities. Cognitive dysfunction is a designated predictor of any neurological disease [1]. Several studies conducted where cognitive dysfunction was evaluated to correlate depression, Epilepsy, Alzheimer's, Parkinson's, and other neurological ailments [2][3][4][5]. Oxidative-stress (OS), a designated source of neurological diseases instigated by endogenic antioxidant system accompanied by cognitive dysfunction. OS generated ROS oxidizes brain macro-molecules and reported a trigger of cognitive abnormalities. Lycopene adopts several antioxidant mechanisms to decrease oxidative stress but due to diminished bioavailability, it fails to express its potential [2][3][4][5]. Although Lycopene shown a lipophilic characteristic due to conjugated system, but its high molecular weight (C40H56=536.87 g/mol) limits its bioavailability. Geometrical isomerism influences its bioavailability as cis-isomers impart thermal stability and higher absorption rate in humans [6,7]. Lycopene absorption also varied with age and diet type, affecting its bioavailability [8][9]with a half-life of 2-3 days [10]. Besides liver it accumulates in adipose tissues, kidneys, lungs, and other lipid-containing organs [6,7]. Several toxicity studies suggested appropriate dose of 5-10 mg/kg, but no toxic effects noticed in rats administered 3 g/kg/day [11]. Cognitive dysfunction is a designated hallmark of diabetic patient hence artificial diabetes develops in rats via streptozotocin (STZ) to gain cognitive model [12]. STZ acts by activating GTS and further favoring superoxide radicals (O2º) generation ( 2 development and dose adjustment to impart an edge for lycopene bio-potentials, but still leaving a lag. Current preliminary research emphasizes on therapeutic potentials of lycopene over cognitive dysfunction at certain doses established via behavioral models.

Materials:
Streptozotocin, Lycopene, Hamilton micro-syringe, 27G needle, citrate buffer, distilled Water procured from Sigma Aldrich, USA, mice food pellet was obtained from local distributor.

Invivo Experiment:
Six groups of 6 albino mice were approved by the institutional ethical committee. Albino mice (20 to 25 gm) were domesticated as standard guidelines (25°C, light, and dark diurnal 12/12 hrs cycle, appropriate food and water) [13].

Dosing:
SCD encompassed 6 groups of 6 animals (already STZ engendered), received lycopene in 0, 10, 50, 100, 150, 200 mg/kg dose via intraperitoneal route in tween-80 suspension. Cognitive activity was measured via Despair test, manual rota-wheel, and Light and dark simulation, 45 minutes post-drug administration. Readings were taken individually and back-to-back switching from one to another model.

Light and dark simulation (RD):
Animal cage (44×21×21 cm) was darkened 1/3 rd black (spray paint), 1/3 rd, and other 1/3 rd was kept in bright LED. Number of crossing from dark to light and vice versa was evaluated in 15 minutes.

Manual Rota-wheel Design (RW):
Animals could rotate wheel, diameter15 cm and thickness 4cm, rotating at their free will, rotations number were assessed in 10 minutes.

Statistical Assessment:
Statistical assessment was handled via one-way analysis of variance (ANOVA) pursued through Dunnett's test. P<0.05, deemed designated as statistically significant, using Graphpad (V9, LLC, USA)

Result and Discussion:-
Lycopene a red, structurally open-chain isomer of β-carotene comprising conjugated (11) and unconjugated (2) double bonds system which imparts a tremendous antioxidant activity towards OS. OS contributes to development of several chronic neurological ailments. Antioxidants act by scavenging free radicals or reactive-oxygen species (ROS), relieving neurodegeneration. Brain often requires consistent oxygen supply and possibly culprit to ROS generation during fail response of intrinsic anti-oxidation system, heading to OS. Intrinsic antioxidant system failure implies improper ROS generation and counteraction [17,18]. Intrinsic oxidases are liable for superoxide radical production, further metabolized to H2O2 and water by other oxidases and peroxidases [19][20][21][22]. STZ actuates neuron's glutamatergic-Transmitter for generation of ROS ( Figure-1) [21,23].
Lycopene scavenges singlet and excited oxygen species and also acts by restoring the functioning of antioxidant enzymes [24], reducing oxidative damage to DNA and biomolecules [25]. Several studies confirmed the safe doses of lycopene as 75 mg/day or ranging 10-120 mg/day. Intake spans prescribed from country to country as 3.7-16.15 mg United States, Germany 0.7-1.3 mg, Canada of 25.2 mg etc. [27]. DT, LD simulation, and RW design are perfect 3 models for Cognitive assessment. DT assess brain alertness reflects by immobility, cognition impairment, accomplishing fast results with high validity and reliability.   Table-1). LD simulation established on light and dark environment exploration. Neuroactive drugs increase crossing number between dark and light compartments. LD simulation often uses to gauge learning, anxiety, and exploration, rodents. LD also employed to test impulsivity, neural systems relevancy. Number of crossing from light to dark or contrariwise for 10 minutes counted as parameter [28].

Disclosure:-
Author states of no conflict of interest