Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model

We conducted an open, add-on study with topiramate (TPM) as adjunctive therapy in Lennox-Gastaut syndrome (LGS), to assess the long-term efficacy and safety and to evaluate quality of life (QL) measurements in the chronic use of TPM. We studied 19 patients (11 male; age ranging from 4 to 14 years) with uncontrolled seizures receiving 2-3 anti-epileptic drugs. Patients were followed up to 36 months of treatment. A questionnaire was used to query parents about QL. Seven patients completed the study at 36 months and seizure frequency was reduced > 75% in 4, and < 50% in 3 patients. Two children became seizure free for more than 24 months. Most side effects were CNS related, with the most frequent being somnolence and anorexia. These were generally transient. One patient dropped-out due to powder in the urine. None of the patients required hospitalization. At 36 months, patients' alertness (2/7), interaction with environment (5/7), ability to perform daily activities (5/7), and verbal performance (6/7) improved on TPM. We conclude that TPM may be useful as adjunctive therapy in the treatment of LGS. The efficacy of TPM was maintained in long-term treatment in more than 40% of patients, long term safety was confirmed and QL improved on TPM.

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Protective effect of Mucuna pruriens against arsenic-induced liver and kidney dysfunction and neurobehavioral alterations in rats

Veterinary World ◽

10.14202/vetworld.2020.1555-1566 ◽

2020 ◽

Vol 13 (8) ◽

pp. 1555-1566

Author(s):

Preethi Concessao ◽

Laxminarayana Kurady Bairy ◽

Archana Parampalli Raghavendra

Keyword(s):

Term Treatment ◽

Seed Extract ◽

Mucuna Pruriens ◽

Memory Retention ◽

Short Term Treatment ◽

Once Daily ◽

Treatment Groups ◽

Long Term Treatment ◽

Liver And Kidney

Background and Aim: Intoxication of arsenic in rats is known to result in neurological effects as well as liver and kidney dysfunction. Mucuna pruriens has been identified for its medicinal properties. The aim of the study was to investigate the protective effect of aqueous seed extract of M. pruriens on sodium arsenite-induced memory impairment, liver, and kidney functions in rats. Materials and Methods: The experiment was divided into short-term treatment (45 days) and long-term treatment (90 days), with each group divided into nine sub-groups consisting of six animals each. Sub-groups 1 and 2 served as normal, and N-acetylcysteine (NAC) controls, respectively. Sub-groups 3-9 received sodium arsenite in drinking water (50 mg/L). In addition, sub-group 4 received NAC (210 mg/kg b.wt) orally once daily, sub-groups 5-7 received aqueous seed extract of M. pruriens (350 mg/kg b.wt, 530 mg/kg b.wt, and 700 mg/kg b.wt) orally once daily and sub-groups 8 and 9 received a combination of NAC and aqueous seed extract of M. pruriens (350 mg/kg b.wt and 530 mg/kg b.wt) orally once daily. Following the treatment, the blood was drawn retro-orbitally to assess the liver (serum alanine transaminase [ALT], serum aspartate transaminase, and serum alkaline phosphatase) and kidney (serum urea and serum creatinine) functions. Learning and memory were assessed by passive avoidance test. Animals were sacrificed by an overdose of ketamine, and their Nissl stained hippocampal sections were analyzed for alterations in neural cell numbers in CA1 and CA3 regions. Results: In the short-term treatment, groups administered with M. pruriens 530 mg/kg b.wt alone and combination of NAC + M. pruriens 350 mg/kg b.wt exhibited a significant improvement in memory retention, less severe neurodegeneration, and decrease in serum ALT levels. In long-term treatment, groups administered with M. pruriens 700 mg/kg b.wt alone and combination of NAC+M. pruriens 350 mg/kg b.wt, respectively, showed better memory retention, decreased neural deficits, and reduced levels of kidney and liver enzymes. Conclusion: The seed extract of M. pruriens showed significant enhancement in memory and learning. The number of surviving neurons in the CA1 and CA3 regions also increased on treatment with M. pruriens. Serum ALT, serum urea, and serum creatinine levels showed significant improvement on long-term treatment with M. pruriens.

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CF3-substituted diselenide modulatory effects on oxidative stress, induced by single and repeated morphine administrations, in susceptible tissues of mice

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0398 ◽

2020 ◽

Author(s):

Renata Fritzsche Rodrigues ◽

Carolina Cristovão Martins ◽

Suzan Rosa ◽

Cristina Wayne Nogueira

Keyword(s):

Oxidative Stress ◽

Antioxidant Properties ◽

Experimental Models ◽

Term Treatment ◽

Organoselenium Compound ◽

Sod Activity ◽

Peripheral Tissues ◽

Long Term Treatment ◽

Liver And Kidney

Studies reveal that oxidative stress is associated with morphine long-term treatment adverse effects. CF3-substituted diselenide (CF3) is a multitarget organoselenium compound that has antioxidant properties in different experimental models. This study aimed to investigate the CF3 effects against redox imbalance in peripheral and central tissues of mice, after single or multiple morphine doses. Swiss male mice received a single dose of morphine (5 mg/kg, s.c) and CF3 (10 mg/kg, i.g), or morphine was repeatedly injected (5 mg/kg, s.c) and CF3 (10 mg/kg, i.g) administered twice daily for 7 days. Oxidative stress was determined in the hippocampus, liver, and kidney. CF3 reversed the increase in reactive species caused by single and multiple morphine doses in the peripheral tissues. CF3 increased hepatic non-protein thiol (NPSH) levels and the superoxide dismutase (SOD) activity decreased by a single morphine dose. CF3 reversed the reduction in SOD activity in the kidney of mice repeatedly exposed to morphine. The study demonstrates that peripheral tissues were more susceptible than the hippocampus to oxidative stress induced by morphine in mice. The results show that CF3 modulated parameters of oxidative stress modified by single and multiple morphine administrations in peripheral and central tissues of mice.

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Technological Challenges in the Development of Optogenetic Closed-Loop Therapy Approaches in Epilepsy and Related Network Disorders of the Brain

Micromachines ◽

10.3390/mi12010038 ◽

2020 ◽

Vol 12 (1) ◽

pp. 38

Author(s):

Bram Vandekerckhove ◽

Jeroen Missinne ◽

Kristl Vonck ◽

Pieter Bauwens ◽

Rik Verplancke ◽

...

Keyword(s):

Closed Loop ◽

Neural Tissue ◽

Term Treatment ◽

Large Area ◽

Suitable Candidate ◽

Long Term Treatment ◽

Liver And Kidney ◽

Surgical Treatments

Epilepsy is a chronic, neurological disorder affecting millions of people every year. The current available pharmacological and surgical treatments are lacking in overall efficacy and cause side-effects like cognitive impairment, depression, tremor, abnormal liver and kidney function. In recent years, the application of optogenetic implants have shown promise to target aberrant neuronal circuits in epilepsy with the advantage of both high spatial and temporal resolution and high cell-specificity, a feature that could tackle both the efficacy and side-effect problems in epilepsy treatment. Optrodes consist of electrodes to record local field potentials and an optical component to modulate neurons via activation of opsin expressed by these neurons. The goal of optogenetics in epilepsy is to interrupt seizure activity in its earliest state, providing a so-called closed-loop therapeutic intervention. The chronic implantation in vivo poses specific demands for the engineering of therapeutic optrodes. Enzymatic degradation and glial encapsulation of implants may compromise long-term recording and sufficient illumination of the opsin-expressing neural tissue. Engineering efforts for optimal optrode design have to be directed towards limitation of the foreign body reaction by reducing the implant’s elastic modulus and overall size, while still providing stable long-term recording and large-area illumination, and guaranteeing successful intracerebral implantation. This paper presents an overview of the challenges and recent advances in the field of electrode design, neural-tissue illumination, and neural-probe implantation, with the goal of identifying a suitable candidate to be incorporated in a therapeutic approach for long-term treatment of epilepsy patients.

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