DSIP

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions.

Omar F Rahman, Steven J Lee, William A Seeds

Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived neurotrophic factor and HGF/c-Met pathways critical to neuroplasticity. Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care.

Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models.

Xiaoxiao Mu, Lijun Qu, Liquan Yin +3 more

Pichia pastoris-secreted delta sleep inducing peptide and crossing the blood-brain barrier peptides (DSIP-CBBBP) fusion peptides holds significant promise for its potential sleep-enhancing and neurotransmitter balancing effects. This study investigates these properties using a p-chlorophenylalanine (PCPA) -induced insomnia model in mice, an approach akin to traditional methods evaluating sleep-promoting activities in fusion peptides.

DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion.

Elena A Tukhovskaya, Elvira R Shaykhutdinova, Alina M Ismailova +6 more

A structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in C57Bl/6 mice. A significant decrease in the myocardial infarction area was registered in KND-treated animals relative to saline-treated control animals (19.1 ± 7.3% versus 42.1 ± 9.2%). The brain infarction volume was significantly lower in animals intranasally treated with KND compared to the control saline-treated animals (7.4 ± 3.5% versus 12.2 ± 5.6%). Injection of KND in the first minute of reperfusion in the models of myocardial infarction and cerebral stroke reduced infarction of these organs, indicating a pronounced cardioprotective and neuroprotective effect of KND and potentiality for the treatment of ischemia-reperfusion injuries after transient ischemic attacks on the heart and brain, when administered during the reperfusion period. A preliminary pilot study using the model of myocardial infarction with the administration of DSIP during occlusion, and the model of cerebral stroke with the administration of KND during occlusion, resulted in 100% mortality in animals. Thus, in the case of ischemia-reperfusion injuries of the myocardium and the brain, use of these peptides is only possible during reperfusion.

Enzymatic attributes of an l-isoaspartyl methyltransferase from Candida utilis and its role in cell survival.

Shakri Banerjee, Trina Dutta, Sagar Lahiri +6 more

Spontaneous deamidation and isoaspartate (IsoAsp) formation contributes to aging and reduced longevity in cells. A protein-l-isoaspartate (d-aspartate) O-methyltransferase (PCMT) is responsible for minimizing IsoAsp moieties in most organisms.

Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke.

Elena A Tukhovskaya, Alina M Ismailova, Elvira R Shaykhutdinova +6 more

Background and Objectives: Mutual effect of the preliminary and therapeutic intranasal treatment of SD rats with DSIP (8 days) on the outcome of focal stroke, induced with intraluminal middle cerebral occlusion (MCAO), was investigated. Materials and Methods: The groups were the following: MCAO + vehicle, MCAO + DSIP, and SHAM-operated. DSIP or vehicle was applied nasally 60 (±15) minutes prior to the occlusion and for 7 days after reperfusion at dose 120 µg/kg. The battery of behavioral tests was performed on 1, 3, 7, 14, and 21 days after MCAO. Motor coordination and balance and bilateral asymmetry were tested. At the end of the study, animals were euthanized, and their brains were perfused, serial cryoslices were made, and infarction volume in them was calculated. Results: Although brain infarction in DSIP-treated animals was smaller than in vehicle-treated animals, the difference was not significant. However, motor performance in the rotarod test significantly recovered in DSIP-treated animals. Conclusions: Intranasal administration of DSIP in the course of 8 days leads to accelerated recovery of motor functions.

Acute mild dim light at night slightly modifies sleep but does not affect glucose homeostasis in healthy men.

Rodrigo Chamorro, Britta Wilms, Annika Holst +6 more

We evaluated the effect of acute mild light exposure at night on sleep architecture and glucose homeostasis.

Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude.

Koustav Roy, Garima Chauhan, Punita Kumari +5 more

Sleep loss at high altitude (HA) play major role in worsening of neuropsychological functions, such as attention, memory and decision making. This study investigates the role of phosphorylated delta sleep inducing peptide (p-DSIP) in improving sleep architecture during chronic hypobaric hypoxia (HH) exposure and restoration of spatial navigational memory.

Expression and Purification of Delta Sleep-Inducing Peptide Fused with Protein Transduction Domain and Human Serum Albumin in Pichia pastoris.

Xin-Guo Zhang, Wen-Na Wang, Chun-Sheng Zhang +3 more

Sleep is a natural part of every individual's life. Delta sleep-inducing peptide (DSIP) is a nonapeptide that could promote sleep through the induction of slow wave sleep. However, little is known about the pharmacological effect of DSIP on insomnia.

Id-1, Id-2, and Id-3 co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy.

Leila Antonângelo, Taila Tuma, Alexandre Fabro +6 more

Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC.

Effect of Delta Sleep-Inducing Peptide on Functional State of Hepatocytes in Rats During Restraint Stress.

I I Bobyntsev, A A Kryukov, A E Belykh +1 more

We studied the effect of delta sleep-inducing peptide (40, 120, and 360 μg/kg intraperitoneally, 1 h before the experiment) on free radical oxidation in the liver, aminotransferase activity, and total serum protein content in male Wistar rats during restraint stress. Treatment with the peptide in a dose of 40 μg/kg increased catalase and superoxide dismutase (SOD) activities and malonic dialdehyde (MDA) concentration in the liver homogenate of animals subjected to acute stress. No significant changes were found after administration of this peptide in other doses. Under conditions of chronic stress, the peptide in a dose of 40 μg/kg caused the most pronounced effect. Catalase and SOD activities and MDA concentration decreased, while aminotransferase activity and protein content remained unchanged under these conditions. Administration of the peptide in a dose of 120 μg/kg was accompanied by a decrease in SOD activity and MDA concentration, increase in total protein content, and reduction of AST activity. Increasing the peptide dose to 360 μg/kg abolished its effects.

Peptides and the blood-brain barrier.

William A Banks

The demonstration that peptides and regulatory proteins can cross the blood-brain barrier (BBB) is one of the major contributions of Dr. Abba J. Kastin. He was the first to propose that peptides could cross the BBB, the first to show that an endogenous peptide did so, and the first to describe a saturable transport system at the BBB for peptides. His work shows that in crossing the BBB, peptides and regulatory proteins act as informational molecules, informing the brain of peripheral events. Brain-to-blood passage helps to control levels of peptides with the brain and can deliver information in the brain-to-blood direction. He showed that the transporters for peptides and proteins are not static, but respond to developmental and physiological changes and are affected by disease states. As such, the BBB is adaptive to the needs of the CNS, but when that adaption goes awry, the BBB can be a cause of disease. The mechanisms by which peptides and proteins cross the BBB offer opportunities for drug delivery of these substances or their analogs to the brain in the treatment of diseases of the central nervous system.

[Antioxidative and detoxifying effects of analogues of delta-sleep inducing peptide (DSIP)].

I I Mikhaleva, V T Ivanov, L V Onoprienko +5 more

16 DSIP analogues with substitutions of 1-2 amino acid residues were synthesized in order to investigate their potential use in medicine. Antioxidative properties of these peptides were studied in vitro and their detoxifying activity was examined in vivo on a model of toxicosis that was induced by the cisplatin cytostatic, which has been widely used in the cancer treatment. Practically all the studied DSIP analogues were shown to exhibit considerable direct antioxidative activity (AOA), and that of the ID-6 analogue was higher than AOA of DSIP and comparable with AOA of vitamin C and β-carotine. This analogue also demonstrated the most pronounced detoxifying effect towards cisplatin action, resulting in a decrease in the animal death from the acute cisplatin toxicity to 17% (in comparison with 50-67% for the control animals) and restoration of a number of cisplatin-sensitive biochemical blood parameters: decrease in the activity of aspartate aminotransferase and alanine aminotransferase and downregulation of the concentration of the final products of nitrogen exchange (creatinine and urea). Thus, the DSIP-relative peptides could be promising agents for the decrease in the toxic effects of cytostatics that are used in oncology.

[THE INFLUENCE OF DELTA SLEEP-INDUCING PEPTIDE ON FUNCTIONAL STATE OF RATS HEPATOCYTES IN FOOT-SHOCK STRESS].

A E Belykh, I I Bobyntsev, A A Kryukov +1 more

The effect of delta sleep-inducing peptide (DSIP) intraperitoneal injection in the doses of 40, 120, 360, and 1080 mcg/kg b. w. on lipid peroxidation and functional hepatocyte state in Wistar male rats subjected to acute and chronic electrical foot-shock stress was investigated. It was observed that 120 mcg/kg peptide normalized the elevation of malondialdehyde (MDA) level in the liver homogenate caused by acute foot-shock stress and also significantly decreased catalase activity in all investigated doses. In serum the injection of DSIP up to 40 mcg/kg increased aminotransferase activity. Peptide in all doses provided the normalization of protein synthetic hepatocyte function, increased catalase and superoxide dismutase activity in chronic stress. In addition malondialdehyde content in the liver homogenate was significantly decreased in the dose of 40 mcg/kg and in other cases it was significantly increased against the background of the common antioxidative activity reduction. The stress-induced increase in serum alanine aminotransferase activity was normalized by peptide administration in the doses of 120, 360, and 1080 mcg/kg.

[Using deltalicin for the treatment of patients with diabetic retinopathy].

N V Kresiun, L S Godlevskiĭ

The characteristics of visual evoked potential (VEP) have been investigated in a group of 15 healthy volunteers (aged 31.7 ± 3.6 years) and 30 insulin-dependent patients (aged 32.1 ± 4.0 years) with diabetes mellitus, among which 15 patients suffered from diabetic retinopathy and 15 patients had no retinopathy. An increase in the latent period along with reduction of the VEP amplitude after photostress action upon the macular part of retina have been observed in patients with diabetes, these effects were more pronounced in the subgroup with retinopathy. The restoration of VEP characteristics in 73.5 ± 3.3 s from the moment of photostress was observed in the control group, while this index in both subgroups of diabetic patients without and with retinopathy was 88.7 ± 5.9 and 137.2 ± 11.3 s, respectively. Treatment with deltalicin (daily dose of 0.0003 g of delta sleep-inducing peptide intranasally for two months) decreased the latent period and led to less pronounced depression of VEP amplitude in patients with diabetic retinopathy, and reduced the period of restoration of VEP characteristics to 95.1 ± 6.8 s.

[Influence of delta-sleep peptide on the enzymes activity of mitochondrial electron transport chain in various rat tissues during aging of the organism].

T I Bondarenko, D S Kutilin, I I Mikhaleva

It is shown that subcutaneous injection of exogenous delta-sleep inducing peptide (DSIP) to rats aged 2-24 months in a dose of 100 μg/kg animal body weight by courses of 5 consecutive days per month has a stabilizing effect on the NADH-dehydrogenase activity in the mitochondrial fractions of various tissues, which together with increasing capacity of the antioxidant system should reduce the production of free radicals and their adverse action on cells macromolecule, herewith the activity of succinate dehydrogenase did not change.

[Influence of delta-sleep inducing peptide on the state of lysosomal membranes and intensity of lysosomal proteolysis in different rat tissues during physiological aging of the organism].

D S Kutilin, T I Bondarenko, I I Mikhaleva

It is shown that subcutaneous injection of exogenous delta-sleep inducing peptide (DSIP) to rats aged 2-24 months in a dose of 100 μg/kg animal body weight by courses of 5 consecutive days per month has a stabilizing effect on the state of lysosomal membranes in rat tissues (brain, heart muscle and liver) at different ontogenetic stages, and this effect is accompanied by increasing intensity of lysosomal proteolysis in these tissues.

Effect of delta sleep-inducing peptide on the expression of antioxidant enzyme genes in the brain and blood of rats during physiological aging.

D S Kutilin, T I Bondarenko, I V Kornienko +1 more

Subcutaneous injections of exogenous delta sleep-inducing peptide in a dose of 100 μg/kg (monthly, 5-day courses) to rats of various age groups (2-24 months) were followed by an increase in the expression of genes for SOD 1 (Sod1) and glutathione peroxidase 1 (Gpx1) in the brain and nucleated blood cells. The expression of these genes was shown to decrease during physiological aging of the body.

Delta-sleep inducing peptide entrapment in the charged macroporous matrices.

Tatiana V Sukhanova, Alexander A Artyukhov, Yakov M Gurevich +4 more

Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2-6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process.

The influence of deltalycyn and transcranial cerebellar stimulation upon recovery of retina after photo stress in patients with diabetic retinopathy.

Nataliya Valentinivna Kresyun

The characteristics of visual evoked potentials (VEP) have been studied in diabetic patients with and without diabetic retinopathy.

[Rat tissues antioxidant status correction by peptide delta sleep during physiological aging of the organism].

T I Bondarenko, D S Kutilin, I I Mikhaleva

It is shown that exogenous delta-sleep inducing peptide increases glutathione antioxidant system level in rat tissues at different stages of ontogenesis, by subcutaneous injection to rats 2-24 months postnatal development in a dose of 100 mg/kg animal body weight by courses of 5 consecutive days per month, and this effect is especially marked in non-renewable postmitotic tissues.

[Effect of deltaran and melatonin on immune system in rats with experimental contact dermatitis].

O O Shandra

The aim of the work was investigation of both humoral and cell-mediated immunity together with leukocytes functional stability indexes in rats with the experimental contact dermatitis (ECD) in conditions of complex pharmacological correction using deltaran and melatonin. Experimental trials were performed under conditions of chronic experiment on model chrome-induced ECD. Both deltaran and melatonin either alone or in combination were used for complex pharmacological correction of humoral and cell-mediated immunity and also for stability of leukocytes. The data obtained showed the expressed disturbances of humoral and cell-mediated immunity and neutrophils' functional stability damage under conditions of chrome-induced ECD in rats. The revealed alterations in functional activity of the immune system were successfully corrected using the combined administration of deltaran and melatonin. The activity of medical complex had exponential character.

[Metabolic effects of delta-sleep inducing peptide during physiological aging of the organism].

T I Bondarenko, E A Maĭboroda, I I Mikhaleva +1 more

Subcutaneous injection of delta-sleep inducing peptide (DSIP) to postnatal rats (aged from 2 to 24 months) during 5 consecutive days every months at a dose of 10 microg/100 g body weight favors normalization of the age-related changes in carbohydrate metabolism and shows hypoglycemic effect, as manifested by a decrease in the level of glycosylated hemoglobin in erythrocytes of test rats. The administration of DSIP in postnatal rats of different age also led to a decrease in serum total lipid level, total cholesterol level, and atherogenicity index and an increase in the level of high-density lipoprotein cholesterol.

[Effects of the δ-sleep inducing peptide on neuronal activity in the dorsal hippocampus of rats with different behavior in the open field after stimulation of the positive and negative emotionalistic structures of the brain].

O S Grigorchuk

We studied the cerebral mechanisms of positive and negative emotions in rats with different behavior in open field, reflecting stress resistance and neuronal effects of delta-sleep-inducing peptide (DSIP). In 20 male Wistar rats 107 neurons of dorsal hippocampus (57 neurons in active in open field--prognostically resistant to emotional stress and 50 inpassive--prognostically predisposed rats) were registered after positive (lateral hypothalamus--LH) and negative (ventromedial hypothalamus--VMH) emotional centers electric stimulation. Hippocampal neurons in active rats were less sensitive to stimulation of LH and VMH compared with passive ones. DSIP microiontophoretic application before LH stimulation decreases neuronal responses in both active and passive animals. DSIP increases dorsal hippocampus neurons sensitivity to VMH stimulation in active rats and decreases in passive ones.

[Olygopeptide KND as a putative endogenous prototype of delta sleep inducing peptide (DSIP). Comparative study of biological properties].

I I Mikhaleva, V T Ivanov, V B Voĭtenkov +2 more

We have undertaken a comparative study on physiological activity of well known neuropeptide DSIP (WAGGDASG E) and new closely related peptide KND (WKGGNASGE) in vivo assays. The sequence of K2, N5-DSIP (KND) was found recently by the computer search for DSIP homologous sequences in available nucleotide and protein databases at 324-332 site of Lysine-specific demethylase 3 B (EC 1.14.11, Swiss-Prot: Q7LBC6.1, 1-1761aa). This human lysine-specific histone demethylase is a representative of the recently discovered family of so called JmjC-domain-containing histone demethylases encoded by JMJD1B gene and ubiquitously expressed in tissues of various mammalian species. Biological investigations performed in this work confirm our preliminary data that DSIP-related peptide KND exhibits the similar biological properties in comparison with DSIP. Assessed by us antioxidative, anticonvulsive and behavioral effects of KND were even more expressed than in DSIP case. These results provide the additional evidences to support our suggestion that KND can be a possible endogenous prototype of "real" DSIP.

[Delta-sleep inducing peptide entrapment and release from polymer hydrogels based on modified polyvinyl alcohol in vitro].

T V Sukhanova, A A Artiukhov, I A Prudchenko +4 more

The aim of the study was to entrap delta-sleep inducing peptide (DSIP) in cross-linked poly(vinyl alcohol)-based hydrogels of different structures and to evaluate peptide release kinetics from these hydrogels using an in vitro model. Isotropic and macroporous hydrogels on the basis of poly(vinyl alcohol) acrylic derivative (Acr-PVA) as well as macroporous hydogels containing epoxy groups which were synthesized by copolymerization of this monomer with glycidyl methacrylate. The isotropic hydrogels were fabricated at positive temperatures while the macroporous hydrogels (cryogels) were prepared at the temperatures below zero. The peptide was entrapped into macroporous modified PVA hydrogels by addition of a peptide solution on previously fabricated matrices, while into PVA-GMA hydrogels containing epoxy groups peptide immobilization was carried out by incubation of hydrogel matrices in the peptide solution. In the case of isotropic hydrogels the peptide was added into the polymer mixture at a hydrogel formation reaction. The peptide release kinetics was studied by incubation of hydrogels in PBS (pH 7.4), in physiological solution (0.9% NaCl) and in water. DSIP concentration in supernatants was determined by phase-reverse HPLC. DSIP release from the macroporous PVA hydrogel after 30 min incubation was 74, 70 and 64% in water, PBS and 0.9% NaCl, relatively, and it was completed in 3 hs. From the isotropic hydrogel the release neither peptide nor products of its degradation was not observed even after 48 hs of incubation. For freshly prepared hydrogel the release kinetics was as follows: 27 and 78% in 30 and 33 hs, relatively. In the case of the lyophilized hydrogel samples the peptide release was 63% in 30 min incubation while drying patterns at room temperature for 3 days resulted in significant peptide loss because its structure damage.

[The diagnostics of adaptive reactions of blood on application the stress-modulating therapy in patients with brain chronic ischemia].

V N Krylov, A V Deriugina, E A Antipenko +1 more

The article deals with the results of analysis of electrophoretic mobility of erythrocytes and leukogram in patients with dyscirculatory encephalopathy on different stages of disease on application therapy with inclusion of stress-modulating pharmaceuticals into course of treatment. It is established that the electrophoretic mobiliy of erythrocytes makes it possible to evaluate the adaptive indicators blood in patients with dyscirculatory encephalopathy. The consideration of these indicators makes feasible the substantiation of inclusion of stress-modulating therapy into complex treatment of patients with chronic cerebrovascular inefficiency.

Neuronal activity in the dorsal hippocampus after lateral hypothalamus stimulation: effects of delta-sleep-inducing peptide.

O S Grigorchuk, P E Umriukhin

We studied central effects of delta-sleep-inducing peptide in the mechanisms of positive emotional state formation in rats. In Wistar rats preliminary tested in an open field, the reactions of 57 neurons of the dorsal hippocampus were analyzed during lateral hypothalamus stimulation and microionophoretic application of delta-sleep-inducing peptide. It was found that the number of neurons not responding to stimulation in the lateral hypothalamus surpassed the number of sensitive neurons (63 and 37%, respectively). Hippocampal neurons in active animals were less sensitive to stimulation of the lateral hypothalamus than in passive rats (33 vs. 42%) After application of delta-sleep-inducing peptide, only 28% neurons responded to stimulation. Thus, delta-sleep-inducing peptide reduced the sensitivity of hippocampal neurons to stimulation of the lateral hypothalamus.

Effect of delta sleep-inducing peptide on oxidative modification of proteins in rat tissues and blood during physiological aging.

T I Bondarenko, I A Sorokina, E A Mayboroda +3 more

Accumulation of oxidized proteins (evaluated by the levels of carbonyl and SH groups) in tissues of 2-24-month-old rats (spleen>myocardium>testicles>liver>skeletal muscles) has been demonstrated. Exogenous delta sleep-inducing peptide injected subcutaneously to rats of different age in a dose of 100 μg/kg by monthly 5-day courses protected proteins of the studied tissues from oxidation; its effect was tissue-specific. Delta sleep-inducing peptide exhibited a hypoglycemic effect: it prevented nonenzymatic glycosylation of hemoglobin and reduced the level of defective protein molecules during aging.

[Effect of delta-sleep inducing peptide on the functional activity of some organs and tissues of rats during physiological aging].

T I Bondarenko, E A Maĭboroda, I I Mikhaleva +1 more

The authors show that exogenous delta-sleep inducing peptide (DSIP) injected subcutaneously to the rats in the age of 2-24 months of postnatal development in a dose of 100 mg/kg of animal body weight in courses for 5 consecutive days every month, has a hepatoprotective effect. DSIP does not affect the functional activity of the pancreas, and is not involved in the regulation of calcium homeostasis in the physiological aging of the organism.

[Sleep peptides in experimental models of epilepsy].

O Stanojlović, D Hrnčić, A Rašić-Marković +3 more