Physiology and Pharmacology
Volume:3 Issue: 2, 1999

Parkinson''s disease (PD) is a human neurodegenerative disorder that is associated with a massive and progressive degeneration of the dopaminergic neurons of the substantia nigra. There is strong evidence that oxidative stress participates in the etiology of PD. Therefore, we designed this study to investigate the neuroprotective activity of vitamin E, a free radical scavenger in the unilateral model of early PD. For this purpose, 6-OHDA lesioned rats were pretreated with d-α-tocopheryl acid succinate (24 I.U./kg, i.m.) and the treatment continued three times a week for a period of one month. Apomorphine- and amphetamine- induced rotations and the number of the WGA-HRP labeled-neurons in the substantia nigra pars compacta were evaluated as indexes of the treatment efficacy. The results of behavioral tests reveal that there is a very significant reduction in drug-induced contraversive (68%) and ipsiversive (74%) rotations in vitamin E-treated lesion group (L+E) compared with the vehicle-treated lesion group (L+V)(p<0.001). Histochemical results indicate that the total number of labelled neurons in the substantia nigra pars compacta show a 30% and 65% decrease in L+E (p<0.05) and L+V groups (p<0.01) respectively compared with the sham group. Taken together, these results suggest that vitamin E is moderately effective in the neuroprotective therapy of Parkinson''s disease and may, at least prolong the survival of nigral dopaminergic neurons.

Tolerance and dependence are two main problems that have limited morphine administration as an analgesic drug and they might be as a result of changes in the number and affinity of receptors, dysfunction of adenylate cyclase, impaired coupling between activated µ receptor and K+ channels, and changes in the K+ and Ca2+ channels. There are several reports concerning the role of some of these factors in the occurrence of tolerance and dependence. It has been suggested that KATP channels are involved in morphine-induced analgesia. In this study the effect of a constitutive KATP opening state by chronic administration of minoxidil (a KATP opener) on morphine tolerance and dependence was studied using tail-flick test. A single dose (5 mg/kg) of morphine, but not its chronic administration produced analgesia (p<0.001). In addition single and chronic (2 mg/kg) administration of minoxidil produced analgesia (p<0.0001 vs ethanol) and chronic co-administration of morphine and minoxidil did not reduce morphine tolerance, while It reduced jumping (p<0.01) and weight loss (p<0.05) as signs of dependence. Naloxone did not antagonize minoxidil analgesia. Morphine analgesia was reduced by glibenclamide 2 mg/kg (p<0.001). These results may suggest that co-administration of morphine and minoxidil is able to reduce some dependence signs of morphine. Since this treatment reduced the jumping and weight loss, but not the writhing sign, it is concluded that different mechanisms and sites of action are involved in the development of each of the dependence signs.

Since the stress influences the biological processes, in the present study the effect of prenatal immobilization stress on the sexual activity of male rats was studied. Adult male and female Wistar rats (Pasteur Institute, Tehran) were copulated. After observing the vaginal plugs, pregnant rats were divided into control and two experimental groups. All groups were kept under the laboratory conditions, i.e. temperature adjusted at 22 ± 2 °C, a light and dark photoperiod of 13:11 hr and special food and water ad libitum. The pregnant control rats were under no stress, but experimental groups were put in the special adjustable restrainers from the beginning of the third week of pregnancy (14th day) which is the development period of the nervous system and the sexual dimorphic nucleus (SDN). One of the experimental groups was immobilized in the restrainer for two hours daily (from 9 to 11 a.m.) and the other for three hours daily (from 8 to 11 a.m.) for one week. The offspring were stayed with their mothers in the same cage for 40 days. Then male young rats (control and experimental groups with 9 rats in each of them) were put in the cages with experienced adult male and receptive female for one day to become familiar with the sexual experience. Then control and experimental male rats were placed individually in cages, each containing a receptive female and their sexual activities were observed. Measurement of serum hormones showed a significant decrease in testosterone level in experimental group compared to the control group that can be attributed to a decrease in the size of SDN and changes in the histology of testis. Also the level of estradiol and progesterone was increased in the experimental group. In addition, the histological study of testis showed a decrease in the number and diameter of seminiferous tubules in experimental groups compared to control. In conclusion, it seems that prenatal immobilization stress affects testicular histology in male rats and also decreases the serum level of testosterone and sexual activities.

Although each subdivision of primary somatosensory cortex (SI) receives dense input from the thalamus, but the exact location and type of information that the fibers convey have not been identified yet. In the present study, the exact source of thalamocortical fibers to areas 2 and 3b was investigated using tract-tracing techniques. Following injection of tracer into area 3b, labeled neurons were only found in the VPL. However, labeled neurons were found in VPL and PoM as well as in LP following tracer injection into area 2. Also less densely labeled neurons were found in CLN, VA, and VL. There were no significant differences in the size of area l-labeled neurons following injection of tracer into areas 3b and/or 2 of VPL. These results indicate that area 2 is involved in the processing of tactile information related to sensorimotor coordination and planning as well as in pain perception.

In the present study the effect of intracerebroventricular (ICV) injection of cerulein, an agonist of CCK receptor and proglumide, a receptor antagonist for hyperalgesia induced by sciatic nerve ligation were investigated in mice. Subcutaneous administration of morphine caused anti-nociception in both intact and nerve-ligated mice. However, the response to opioids was lower in ligated mice as compared to the intact animals. Cerulein induced antinociception only in the nerve-Iigated animals. Combination of cerulein with morphine elicited higher response in both intact and ligated animals. However, the induced response was much prominent in ligated animals. Proglumide alone did not elicit any response in both groups. The antagonist decreased the response of cerulein in the non-ligated mice. In addition a low dose of proglumide in combination with cerulein induced antinociception in the ligated mice. It can be concluded that CCK receptor-related

While the effect of changes of stimulus waveform (quasitrapezoidal and rectangular current pulses) on nerve activation is clear, but there is no evidence on the effect of quasitrapezoidal pulses on ionic currents of cellular membrane. In the present study, the effect of depolarizing quasi-trapezoidal current pulses, in comparison with that of depolarizing rectangular current pulses, on firing behavior of isolated Fl neuron in Helix aspersa was investigated using intracellular recording technique (current clamp). In standard ringer, increasing the intensity of quasi-trapezoidal pulses, in comparison with rectangular pulses, caused a considerable rise of the amplitude and the duration of elicited action potential. The reduction of time constant of fast afterhyperpolarization (fAHP) and post-stimulus hyperpolarization (PSH) after injection of low intensity of quasi-trapezoidal pulses was significantly more than that of rectangular pulses. After elimination of K+ and Na+ currents, a low intensity of quasi-trapezoidal stimulus caused a 12 % decrease in the amplitude of high-threshold Ca2+ spikes. On the other hand, with an increase in the threshold of action potential, the time constant of PSH and reduction in the threshold latency through quasi-trapezoidal pulses was more than rectangular pulses. In the presence of nifedipine (1 mM), no significant differences were observed between the effects of two waveforms of stimulus on firing behavior. The results of this study showed that two waveforms of stimulus have different effects on firing behavior and ionic nonlinear currents in FI neuron. It seems that the quasitrapezoidal pulses, through slowing hyperpolarization of membrane potential can increase the cell excitability.

Iontophoresis is one of the skin permeation enhancement methods involving the transport of drugs through the skin under the effect of electrical current. The effect of molecular charge on the iontophoretic permeation of drugs has not been completely understood yet. Therefore the effect of passive and iontophoretic permeation of L-phenylalanine at pH 3.6 (positive charge) and pH 8 (negative charge) with the same charge concentrations was studied through cellulose acetate membrane (CA). The results revealed that there is a significant difference (p = 0.025) between passive (0.92 ± 0.11 mg/cm2/hr) and iontophoretic (1.08 ± 0.07 mg/cm2/hr) fluxes at pH 3.6. However, there was no difference (p = 0.208) between passive (1.06 ± 0.11 mg/cm2/hr) and iontophoretic (1.13 ± 0.12 mg/cm2/hr) fluxes at pH 8. This should be due to the presence of electroosmotic flow at pH 8, which its direction is opposite to that of ions that are moving under the direct effect of the electrical current. These results are in agreement with our previous data and show that CA can model the effects of electroosmotic flow on the iontophoretic permeation of drugs through the skin. Our investigations also show that efficiency of iontophoresis for positive and negative ions are different practically. The results also indicate that there is no difference between fluxes at pH 3.6 and 8 in either passive (p = 0.119) or iontophoretic (p = 0.499) methods. These data are opposite to that of our previous results that showed the fluxes at pH 3.6 are significantly less than that of pH 8 in both methods. This should be due to charge and size-dependent differences of skin and CA and imply that CA can not quantitatively model the skin barrier in this regard.

Urinary N-acetyl-β-D-glucosalninidase (NAG) has been proved to be a useful marker of early renal injury as a result of factors such as lead toxicity. In this study the effect of lead acetate on the kidney and its correlation with the nitric oxide (NO) system was investigated by determining the NAG release in perfused kidney of rat. Lead acetate caused a time- and dose-dependent increase in enzymuria. The effect of concurrent perfusion with lead and arginine (L-Arg) or L-NG-nitro arginine methyl ester (L- NAME) (precursor of NO and inhibitor of NO synthase respectively) in the perfusion fluid was also studied by measuring NAG activity in the perfusate of rat kidney. L-Arg (2 mM) decreased (p<0.001) and L-NAME (0.1 mM) increased significantly the lead-induced enzyme release from the kidney in a time-dependent manner. Moreover, histological studies by light microscope showed that some of the epithelial cells in the proximal convoluted tubules are degenerated or necrotic and desquamated into the lumens in rats treated with lead acetate. This change occurs at a concentration of 50 µg/dl for lead acetate and is increased in the presence of L-NAME. However, an addition of L-Arg had no effect on histological indicators of lead nephrotoxicity. This may suggest that lead may interfere with the NO system in the kidney of rat.

Impaired wound healing is a well-documented complication in diabetes mellitus. With respect to the mechanism involved in impairment of wound healing in diabetic subjects and also the biological effects of fish oil and ω-3 fatty acids, in this study it was tried to examine whether fish oil-rich diet accelerates wound healing in diabetic rats or not? The adult male rats were divided into six groups. Group I (normal) consisted of normal rats, Group II (control) which received alloxan monohydrate, groups III (fish oil group) and IV (corn oil group or placebo) consisted of rats made diabetic by the alloxan (150 mg/kg s.c.) injection. Groups V and VI consisted of normal rats, which treated with fish oil or corn oil respectively. Groups III and V received 1.6 ml/day of fish oil, and groups IV and VI received 1.6 ml/day of corn oil in the pre- and post-operative days. All animals were wounded by a vertical 4 cm incision in the midline of dorsum. Wound surface area measured at days 0, 2, 5, 10, and 15 of post-operative period. Surface area of the wound in group III was less than group II (p<0.05) and group IV (p<0.05), in all of the post-operative days. Surface area of the wound in group III was the same as group V. Surface-area of the wound in group VI was more than group I (p<0.05). Percentage of wound healing in group III was more than groups II and IV (p<0.05). Healing time was less in group III compared to groups II and IV. These data suggest that fish oil (rich in ω-3 fatty acids), but not corn oil can accelerate wound healing.

There are several reports on the therapeutic effects of TFG in Iranian traditional medical literature such as antinociceptive, antipyretic, and anti-inflammatory, antidiabetic and antidiuretic effects. The anti-inflammatory and anti-pyretic effects of TFG have been confirmed in experimental models. In the present study, the antinociceptive effect of TFG extract in formalin and tail flick tests and its site of action were investigated on NMRI rats (220 ± 20 g). The TFG extract was administered by three routes, i.e. i.c.v., i.t. and i.p. at different doses. The effect of i.p. administration was also examined in tail flick test. The results showed that i.p. administration of aqueous extract of TFG leaves induced analgesia in tail flick and both phases of formalin test. The i.t. administration at doses of 0.5, 1, 2 and 3 mg/rat showed significant antinociceptive effect in formalin test, however i.c.v. administration of extract had no antinociceptive effect. The results of the present study supported the facts that: 1) TFG extract has antinociceptive effect in first and second phases of formalin and tail flick tests and 2) the site of its action in the first and second phase of formalin test might be at spinal cord and with regard to its anti-inflammatory effect, peripheral mechanisms may be involved in its analgesic effect in the second phase of formalin test.

Tannins are plant-derived polyphenolic compounds that are widely found in foods, particularly in fruits and beverages. These materials are water-soluble and able to precipitate proteins from aqueous solutions. It had been shown that feeding some animals such as rat and mouse with tannins mimicks the effects of isoproterenol on salivary glands. Tannins stimulate β-receptors by some indirect mechanisms. In the present study, two groups of male Guinea pigs (Cavia porecellus) were selected. The first group was fed with diets high in tannins for 20 days and the second group was chosen as control. After using tannins, both parotid and submandibular glands revealed a significant increase in weight. Biochemical studies indicated that tannins decreased the amount of total protein and amylase in parotid gland, but on the other hand in submandibular gland, total protein and amylase increased. Sodium dodecylsulfate polyacrylamide gel electrophoresis from parotid gland showed three protein bands with molecular weights of 67, 52 and 14 Kds that were weakly stained as compared to control ones. Extracted protein from tannin-treated submandibular gland showed protein bands with molecular weights of about 67, 52 and 16.5 Kds respectively. These bands were stronger than control group. It seems that protein bands with molecular weights of about 67, 16.5 and 14 Kds belong to a group of proline-rich proteins. Protein band with molecular weight of about 52 Kd probably belongs to amylase. These differences probably indicate that the number of β1- and β2-adrenergic receptors may be varied in both parotid and submandibular secretory cells. On the other hand, it seems that β1-receptors are mainly present in parotid gland, but in submandibular gland, β2-receptors are predominant.