Haematological and Biochemical Changes in Response to Stress Induced by the Administration of Amikacin Injection by Autoinjector in Animals

Objective: The objective of the present study was to evaluate the safety and tolerability of autoinjector devices (AIDs) in rabbits by intramuscular (i.m.) administration, using haematological and biochemical markers. Introduction: Emergency and mass casualty situations require immediate drug delivery for which AIDs are preferred. The tolerability of amikacin as antibacterial and buprenorphine as analgesic AID has been studied in rats by intraperitoneal administration. In the present study, it was evaluated in rabbits by i.m. administration. Methods: Water-filled glass cartridges (2.3–2.4 mL) were converted to amikacin (106 mg/mL) and buprenorphine (0.128 mg/mL) cartridges. Dual dose AID was used for i.m. administration (1.2 mL). The study was done as a crossover design on 12 rabbits. Initially, three rabbits each were given manually or AID, 57 mg/kg amikacin, and three rabbits each by manual or by AID, 0.07 mg/kg buprenorphine for 7 days. After 1 month, the injections were changed in the rabbits. In the place of manual injection, AID and in the place of amikacin, buprenorphine injection was given. This ensured that all rabbits received 14 injections, 7 manual and 7 AID consisting of 7 amikacin and 7 buprenorphine. 24 h before and 24 h after last drug administrations, blood was withdrawn from ear vein for haematological and biochemical estimations. Results: The rabbits were healthy, active and no sign of any injection-related changes were observed after administration of amikacin and buprenorphine by manually or by AID. The haematological and biochemical parameters showed similar changes in manual and AID administration of amikacin and buprenorphine. Conclusion: The present study of amikacin and buprenorphine by AID shows the safety of the device and is recommended for further experimentation. These AIDs are intended for self-administration during emergency and mass causality situation and are suitable for adults and children, as well as farm and pet animals.

show abstract

“…injection for the tolerability. 9 , 13 , 17 Hence, the present study was carried out in rabbit model.…”

Section: Discussionmentioning

confidence: 99%

Safety evaluation of antibacterial and analgesic autoinjector devices for rapid administration during emergency situations: a crossover study in rabbits

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Animal experimentation and grouping were performed as per approved institutional guidelines. 22, 23 The development of PD symptoms such as bradykinesia, postural instability, gait disturbances, and rigidity was carefully monitored twice daily. The animals were anaesthetised with isoflurane when they developed debilitating behavioural changes, i.e., limiting mobility, feeding, or grooming (Raman and Weil, Mumbai).…”

Section: Animal Grouping and Experimental Protocolmentioning

confidence: 99%

Biochemical and Neurobehavioral Changes in the Rat Model of Parkinson�s Disease with Suprathreshold Exercise and Usnic Acid

Kumar¹,

Sivanesan²,

Nair³

et al. 2023

Int J Life Sci Pharm Res

View full text Add to dashboard Cite

Finding a solution for Parkinson's disease has been a challenge to researchers despite advances in medicinal research. None of the options available so far has been able to reverse dopaminergic damage or increase endogenous dopamine production from existing dopaminergic cells in Parkinson's disease. Research in Parkinson’s disease has not so far resulted in finding better solutions for reversing dopaminergic damage or increasing dopamine production. Above-the-threshold (suprathreshold) exercises producing improvement have been documented with supporting clinical and imaging findings but without any biochemical evidence. Above-the-threshold (suprathreshold) exercises producing improvement in Parkinson's disease have been documented with supporting clinical and imaging findings. To the best of our knowledge, the biochemical basis of this improvement has not been studied in detail. Recently, biomolecules like usnic acid have been shown to improve dopamine levels through protective and regenerative effects. This study aimed at understanding the biochemical basis of the improvement following suprathreshold exercises and usnic acid. The objectives were to assess whether the suprathreshold exercise produces improvement in PD rat models and, if so, to understand the biochemical basis of improvement and compare the mechanism with that of usnic acid.The effect of suprathreshold exercise and usnic acid on Parkinson’s disease Hence, this study was conceived to understand whether the exercise produces results due to a similar mechanism that had never been reported before. Parkinson's disease was compared with rotenone alone, rotenone and high-fat diet models, and control. Induced with rotenone and a high-fat diet, the effect of suprathreshold exercise was compared to that of usnic acid, the rotenone alone model, and control. Locomotor behaviour was assessed with an actophotometer and rotarod. Western blotting assessed the blood biochemical parameters, antioxidant and dopamine levels in addition to α-synuclein, tyrosine hydroxylase, Nurr1, and HSP70 levels. Usnic acid decreased oxidative stress markers like MDA, peroxynitrite and nitric oxide, indicating lesser oxidative stress, increased dopamine and serotonin levels and decreased α-synuclein expression. But the suprathreshold exercise did not significantly affect oxidative stress markers nor increased dopamine levels. However, α-synuclein expression was decreased. Compared with usnic acid, lower Nurr1 levels in the suprathreshold group demonstrate lesser protective and regenerative effects on dopaminergic neurons. HSP70 levels indicate that improvement in suprathreshold exercise resulted from preventing misfolding of α-synuclein or through a noncanonical interaction, and comparable locomotor behaviour was observed in both groups. Biomolecules like brain-derived neurotropic factors produced by suprathreshold exercises acting centrally and in muscles might have also contributed to improvement in this group. When usnic acid increased dopamine levels in the brain through protective effects on dopaminergic neurons, antioxidant effects, and reduced expression of α-synuclein, suprathreshold exercise did not increase dopamine, decreased α-synuclein and had less antioxidant effects. This study biochemically proves that suprathreshold exercise alleviates Parkinson’s disease symptoms by preventing α-synuclein misfolding and not by mechanisms other than increasing dopamine, neuroprotection or regeneration of dopaminergic neurons, which require further studies in humans.

show abstract

“…All the groups were to receive drugs for at least 21 days. Animal experimentation and grouping were performed per approved institutional guidelines 6,24 .…”

Section: Animal Grouping and Experimental Protocolmentioning

confidence: 99%

Untitled

2023

IJPSR

View full text Add to dashboard Cite

Parkinson's disease has been a challenging neurodegenerative disorder for researchers and clinicians alike for decades. Though L-dopa has changed the management of PD to a considerable extent, effective solutions remain elusive since L-dopa, after a few years, partly loses its efficacy and develops dyskinesias as a complication, incapacitating the patient. Also, existing PD animal models using MPTP, rotenone, paraquet, etc cause significant suffering to the animals and also require a minimum of 22-25 days for induction. Hence, a better PD animal model was conceived considering the synergistic oxidative stress lipids, and rotenone induce on striatal neurons. The experiment compared the existing rotenone induction with combined rotenone and high-fat diet induction, carefully watching for motor and behavioural symptoms of PD in the Wistar rats in addition to measuring the biochemical profiles for toxicity, strictly following the ARRIVE guidelines for animal research. This study found that using HFD+Rot for induction not only shortened the duration of induction to a mean of 14 days but also reduced the suffering by reducing the number of intraperitoneal injections needed without significant derangement of safety biochemical parameters. This study also proves the effectiveness by demonstrating the reduced dopamine, serotonin levels in striatal neurons and increased oxidative stress parameters. To the best of our knowledge, no animal study shows a better PD model with all the neurobehavioural and biochemical features of PD with less time for induction. This new HFD+Rot model can therefore be employed to test therapeutics and neurobehavioural studies.

show abstract

Haematological and Biochemical Changes in Response to Stress Induced by the Administration of Amikacin Injection by Autoinjector in Animals

Cited by 7 publications

References 12 publications

Safety evaluation of antibacterial and analgesic autoinjector devices for rapid administration during emergency situations: a crossover study in rabbits

Safety evaluation of antibacterial and analgesic autoinjector devices for rapid administration during emergency situations: a crossover study in rabbits

Biochemical and Neurobehavioral Changes in the Rat Model of Parkinson�s Disease with Suprathreshold Exercise and Usnic Acid

Untitled

Contact Info

Product

Resources

About